Multicancer detection (MCD) tests use a single biospecimen, such as blood, to screen for multiple cancers simultaneously. These tests aim to improve early cancer detection, particularly for cancers without current screening methods. However, their benefits and harms are not well understood. MCD tests differ from conventional screening tests because the organ of origin is unknown, requiring further diagnostic workup. Two prospective studies involving over 16,000 individuals found that MCD tests identified cancers in early stages, including pancreas, ovary, liver, uterus, small intestine, oropharyngeal, bone, thyroid, and hematologic malignancies. Reported sensitivities range from 27% to 95%, but are lower for early-stage cancers. False reassurance from negative results may reduce screening adherence, risking public health benefits. Prospective clinical trials are needed to evaluate MCD accuracy, early detection potential, overdiagnosis, and equitable use across populations. MCD tests are not simple blood tests but screen for cancer without a definitive diagnosis. Further diagnostic workup is needed for positive results, posing potential harms from invasive procedures. Evaluation of MCD tests is challenging due to knowledge gaps and new frameworks. Federal regulations do not require clinical utility for MCD tests, allowing them to be introduced as laboratory-developed tests without FDA review. MCD tests use biomarkers like ctDNA, circulating tumor cells, and extracellular vesicles to detect cancer. They are complex, involving multiple molecular analytes and sophisticated algorithms. MCD tests are in early development stages, with some in prospective screening phases. The Pathfinder study found that 92 out of 6662 participants had a positive MCD signal, with 35 true positives. The DETECT-A study found 8 early-stage cancers detected by MCD tests. The UK Galleri trial is evaluating MCD screening's impact on cancer mortality. The NCI is funding research to assess MCD tests' clinical utility. MCD tests have potential to reduce health disparities but may worsen them if access to diagnostic testing is limited. MCD tests may lead to overdiagnosis and overtreatment, and their benefits are uncertain. Clinical trials are needed to determine their effectiveness and safety. MCD tests offer potential for early cancer detection but require further research to ensure they are effective and safe for widespread use.Multicancer detection (MCD) tests use a single biospecimen, such as blood, to screen for multiple cancers simultaneously. These tests aim to improve early cancer detection, particularly for cancers without current screening methods. However, their benefits and harms are not well understood. MCD tests differ from conventional screening tests because the organ of origin is unknown, requiring further diagnostic workup. Two prospective studies involving over 16,000 individuals found that MCD tests identified cancers in early stages, including pancreas, ovary, liver, uterus, small intestine, oropharyngeal, bone, thyroid, and hematologic malignancies. Reported sensitivities range from 27% to 95%, but are lower for early-stage cancers. False reassurance from negative results may reduce screening adherence, risking public health benefits. Prospective clinical trials are needed to evaluate MCD accuracy, early detection potential, overdiagnosis, and equitable use across populations. MCD tests are not simple blood tests but screen for cancer without a definitive diagnosis. Further diagnostic workup is needed for positive results, posing potential harms from invasive procedures. Evaluation of MCD tests is challenging due to knowledge gaps and new frameworks. Federal regulations do not require clinical utility for MCD tests, allowing them to be introduced as laboratory-developed tests without FDA review. MCD tests use biomarkers like ctDNA, circulating tumor cells, and extracellular vesicles to detect cancer. They are complex, involving multiple molecular analytes and sophisticated algorithms. MCD tests are in early development stages, with some in prospective screening phases. The Pathfinder study found that 92 out of 6662 participants had a positive MCD signal, with 35 true positives. The DETECT-A study found 8 early-stage cancers detected by MCD tests. The UK Galleri trial is evaluating MCD screening's impact on cancer mortality. The NCI is funding research to assess MCD tests' clinical utility. MCD tests have potential to reduce health disparities but may worsen them if access to diagnostic testing is limited. MCD tests may lead to overdiagnosis and overtreatment, and their benefits are uncertain. Clinical trials are needed to determine their effectiveness and safety. MCD tests offer potential for early cancer detection but require further research to ensure they are effective and safe for widespread use.