• Participants with a cancer diagnosis: Documentation of disease:

‣ Histologic documentation: Histologically confirmed diagnosis of invasive cancer

⁃ Stage: Stage I-IV per American Joint Committee on Cancer (AJCC) 7th edition, with the exception of patients with leukemia, lymphoma, and multiple myeloma

• For leukemia: Type (chronic lymphocytic leukemia \[CLL\], chronic myeloid leukemia \[CML\], acute lymphoblastic lymphoma \[ALL\], acute myeloid leukemia \[AML\])

∙ For lymphoma: Stage I-IV based on Ann Arbor staging

∙ For multiple myeloma: Stage I, II, III based on Revised International Staging System (RISS)

⁃ One of the following tumor types:

• Colorectal

∙ Bladder

∙ Head and neck

∙ Hepatobiliary

∙ Lung

∙ Lymphoma

∙ Leukemia

∙ Ovary \*\*\* For these specific cancer types only, patients may be enrolled prior to histologic confirmation of malignancy. Sites are required to contact the study chairs to review appropriateness for enrollment

∙ Pancreas \*\*\* For these specific cancer types only, patients may be enrolled prior to histologic confirmation of malignancy. Sites are required to contact the study chairs to review appropriateness for enrollment

∙ Multiple myeloma

∙ Gastric, esophageal or gastroesophageal

∙ Breast

∙ Thyroid

∙ Kidney

⁃ For these specific cancer types only, patients may be enrolled prior to histologic confirmation of malignancy. Sites are required to contact the study chairs to review appropriateness for enrollment

∙ Endometrium

∙ Prostate

∙ Melanoma

• \*\*\* For these specific cancer types only, patients may be enrolled prior to histologic confirmation of malignancy. Sites are required to contact the study chairs to review appropriateness for enrollment

∙ Sarcoma

• Participants with a cancer diagnosis: No prior definitive systemic or local anti-cancer intervention

• Participants with a cancer diagnosis: Age \>= 40 and =\< 75

• Participants with a cancer diagnosis: No known current pregnancy by self-report

• Participants with a cancer diagnosis: No known or prior history of in situ or invasive malignancy (excluding in situ non-melanoma skin cancers) other than the current cancer diagnosis

• Participants with a cancer diagnosis: Willingness to provide blood samples for research use

• Participants with a cancer diagnosis: Absence of medical contraindications to a research blood draw volume of 60 mL

• Participants with a cancer diagnosis: No history of organ transplantation

• Participants with a cancer diagnosis: Ability to read and comprehend English or Spanish

• \* Eligibility is restricted to individuals who can comprehend and read English or Spanish given that participation in the study will require the ability to read and complete questionnaires that are available only in those two languages

• Participants without a cancer diagnosis and without suspicion of cancer: Age \>= 40 and =\< 75

• Participants without a cancer diagnosis and without suspicion of cancer: No known current pregnancy by self-report

• Participants without a cancer diagnosis and without suspicion of cancer: No known or prior history of in situ or invasive malignancy (excluding in situ non-melanoma skin cancers)

• Participants without a cancer diagnosis and without suspicion of cancer: Willingness to provide blood samples for research use

• Participants without a cancer diagnosis and without suspicion of cancer: Absence of medical contraindications to a research blood draw volume of 60 mL

• Participants without a cancer diagnosis and without suspicion of cancer: No history of organ transplantation

• Participants without a cancer diagnosis and without suspicion of cancer: Ability to read and comprehend English or Spanish

• \* Eligibility is restricted to individuals who can comprehend and read English or Spanish given that participation in the study will require the ability to read and complete questionnaires that are available only in those two languages

• Participants with a high suspicion of cancer: High suspicion of ovarian cancer, pancreatic cancer, kidney cancer, or melanoma by clinical and/or radiological assessment, with plans for histologic or cytologic confirmation within 28 days after study blood draw

• \* Examples of highly suspicious cases include: elevated CA125 and abnormal transvaginal ultrasound, suspicious renal or pancreatic mass on imaging, suspicious cutaneous lesion concerning for melanoma

• Participants with a high suspicion of cancer: Central review of radiology reports and/or clinical documentation conducted by study chairs

• Participants with a high suspicion of cancer: Age \>= 40 and =\< 75

• Participants with a high suspicion of cancer: No known current pregnancy by self-report

• Participants with a high suspicion of cancer: No known or prior history of in situ or invasive malignancy (excluding in situ non-melanoma skin cancers) other than the current cancer diagnosis

• Participants with a high suspicion of cancer: Willingness to provide blood samples for research use

• Participants with a high suspicion of cancer: Absence of medical contraindications to a research blood draw volume of 60 mL

• Participants with a high suspicion of cancer: No history or organ transplantation

• Participants with a high suspicion of cancer: Ability to read and comprehend English or Spanish \* Eligibility is restricted to individuals who can comprehend and read English and Spanish given that participation in the study will require the ability to read and complete questionnaires that are available only in those two languages