A 37-year-old woman with abnormal cell-free DNA (cfDNA) results in her second pregnancy was later diagnosed with stage IV colon cancer. The initial cfDNA test suggested full or partial monosomies for chromosomes 13, 18, 21, and X. However, diagnostic testing by amniocentesis showed a normal karyotype. Further analysis of the cfDNA results revealed a "saw-tooth" pattern, suggesting genome-wide imbalance, which raised suspicion of maternal malignancy. A postpartum MRI scan identified multiple liver lesions, and subsequent imaging confirmed the presence of metastatic colon cancer. The patient underwent surgery and chemotherapy but ultimately died 10 months postpartum. The infant was healthy. The case highlights the importance of investigating discordant cfDNA results, as they may indicate maternal malignancy. The cfDNA test results were influenced by excess DNA sequences from reference chromosomes, leading to false monosomy readings. The patient's genome-wide data showed multiple abnormalities, suggesting malignancy. However, targeted sequencing methods that do not use ratios may not detect such abnormalities. This case is part of a growing body of evidence showing that discordant cfDNA results can be linked to metastatic cancer in pregnant women. Other cases have been reported where discordant results led to the diagnosis of ovarian carcinoma, follicular lymphoma, and Hodgkin lymphoma. The current recommendations for evaluating malignancy in the setting of discordant cfDNA results are based on expert opinions and include obtaining a complete blood count, chemistry panel, and whole-body MRI scan. The management of pregnant women with discordant cfDNA results remains a clinical challenge, particularly when genome-wide sequencing suggests malignancy. The most common cancers diagnosed in pregnant women include breast, cervical, Hodgkin lymphoma, leukemias, and malignant melanoma. These are also the most common types of cancers seen in women of reproductive age. As more information becomes available, specific cfDNA test result patterns may be helpful in guiding the subsequent evaluation. The extent of the diagnostic work up may be limited by the pregnancy itself. Standard serologic tumor markers are unreliable in a pregnant woman.A 37-year-old woman with abnormal cell-free DNA (cfDNA) results in her second pregnancy was later diagnosed with stage IV colon cancer. The initial cfDNA test suggested full or partial monosomies for chromosomes 13, 18, 21, and X. However, diagnostic testing by amniocentesis showed a normal karyotype. Further analysis of the cfDNA results revealed a "saw-tooth" pattern, suggesting genome-wide imbalance, which raised suspicion of maternal malignancy. A postpartum MRI scan identified multiple liver lesions, and subsequent imaging confirmed the presence of metastatic colon cancer. The patient underwent surgery and chemotherapy but ultimately died 10 months postpartum. The infant was healthy. The case highlights the importance of investigating discordant cfDNA results, as they may indicate maternal malignancy. The cfDNA test results were influenced by excess DNA sequences from reference chromosomes, leading to false monosomy readings. The patient's genome-wide data showed multiple abnormalities, suggesting malignancy. However, targeted sequencing methods that do not use ratios may not detect such abnormalities. This case is part of a growing body of evidence showing that discordant cfDNA results can be linked to metastatic cancer in pregnant women. Other cases have been reported where discordant results led to the diagnosis of ovarian carcinoma, follicular lymphoma, and Hodgkin lymphoma. The current recommendations for evaluating malignancy in the setting of discordant cfDNA results are based on expert opinions and include obtaining a complete blood count, chemistry panel, and whole-body MRI scan. The management of pregnant women with discordant cfDNA results remains a clinical challenge, particularly when genome-wide sequencing suggests malignancy. The most common cancers diagnosed in pregnant women include breast, cervical, Hodgkin lymphoma, leukemias, and malignant melanoma. These are also the most common types of cancers seen in women of reproductive age. As more information becomes available, specific cfDNA test result patterns may be helpful in guiding the subsequent evaluation. The extent of the diagnostic work up may be limited by the pregnancy itself. Standard serologic tumor markers are unreliable in a pregnant woman.