This is a prospective, multi-center interventional study of the GRAIL multi-cancer early detection (MCED) test with return of test results for participants enrolled through healthcare systems in North America. The purpose of this study is to evaluate the safety and performance of the GRAIL MCED test in a population of individuals who are eligible for guideline-recommended cancer screening. In cases with a "cancer signal detected" test result, participants will undergo diagnostic procedures based on the test returned cancer signal origin(s) to determine if they have cancer. The number and types of diagnostic procedures required to achieve diagnostic resolution will be assessed. Participant-reported outcomes will be collected at several time points to assess participants' perceptions about the multi-cancer early detection test.

The study will enroll approximately 35,000 and no more than 38,500 participants as defined by eligibility criteria over an anticipated enrollment period of approximately 36 months at up to 40 clinical institutions within North America. Participants will be actively followed for approximately 3 years from the date of their enrollment.

Inclusion Criteria:

1. Participants must be at least 50 years of age, inclusive, at the time of signing the Informed Consent Form (ICF).
2. Participants must be capable of giving signed and legally effective informed consent

Exclusion Criteria:

1. Undergoing or referred for diagnostic evaluation due to clinical suspicion for cancer (e.g., referred to a medical or surgical oncologist, or scheduled for biopsy on the basis of a suspicious imaging abnormality).

2. Personal history of invasive solid tumor or hematologic malignancy, diagnosed within the 3 years prior to expected enrollment date, or diagnosed greater than 3 years prior to expected enrollment date and never treated.

   • Individuals with a diagnosis of non-metastatic basal cell carcinoma and squamous cell carcinoma of the skin are not excluded.

3. Prior/Concurrent Concomitant Therapy (Medications/Treatments):

   • Definitive treatment for invasive solid tumor or hematologic malignancy within the 3 years prior to expected enrollment date. Adjuvant hormone therapy for cancer (e.g. for breast or prostate cancer) is not an exclusion criterion.

4. Individuals who will not be able to comply with the protocol procedures.

5. Individuals who are not currently registered patients at a participating center.

6. Previous or current participation in another GRAIL-sponsored study. "Participation" is defined as having signed consent and provided a blood sample.

7. Previous or current employees or contractors of GRAIL.

8. Current pregnancy (by self-report of pregnancy status)