Noninvasive prenatal testing (NIPT) or cell-free DNA (cfDNA) screening can be used to screen for common fetal autosomal aneuploidies. However, NIPT is not a diagnostic test, as cfDNA in the plasma of pregnant women contains a mixture of placental and maternal DNA. Noninvasive prenatal testing or cfDNA testing can therefore differ from results of the direct fetal karyotype. A single case report in 2013 reported that maternal cancer could be a reason for NIPT discordance. In this current study, the authors retrospectively examined DNA sequencing data in a series of pregnant women (n = 3757) with abnormal NIPT results (≥1 aneuploidies involving chromosomes 13, 18, 21, X, or Y), in order to determine if there is a relationship between maternal malignancy and NIPT discordance. Of the 3757 women, 10 received a diagnosis of cancer after screening. Of these cancer cases, which were clinically diverse (early stage to metastatic disease), 2 women declined to participate in the study because of severe disease. Genome-wide bioinformatics analysis was performed on the remaining 8 asymptomatic women, which showed that copy-number variants spanned 4% to 44% of the genome in these women, with consistent copy-number changes involving multiple chromosomes and focal amplifications or deletions to whole chromosomes. In 7 of these cancer cases, diagnostic fetal karyotyping showed euploid results (46, XY or 46, XX). In regard to aneuploidy patterns in maternal cancer, 7 (18%) of 39 cases in which NIPT reported multiple aneuploidies were in women who were found to have occult cancer; 35 of these NIPT results were confirmed to be false positive in which the fetal karyotype was normal. However, follow-up information for 19 of these 35 cases was incomplete. The authors thus estimated the risk of maternal cancer in this subset in the following manner. If cases in which follow-up information was unavailable were concordant with fetal karyotype, then risk of maternal cancer, as an explanation for discordant results, would be 44% (7 of 16). If these cases were discordant with the fetal karyotype, risk would be 20% (7 of 35). In summary, if multiple aneuploidies are detected, then risk of maternal cancer is between 20% and 44%. Although the sample size was very small, this study showed that occult maternal malignancy may provide a biological explanation for some discordant NIPT results, caused by cfDNA being released into maternal circulation by apoptotic malignant cells. However, further research is needed to ascertain the clinical importance of these findings.