Cell-free DNA screening for fetal aneuploidy is a commonly used testing strategy in pregnancies at high risk for fetal aneuploidy. The use of cell-free DNA screening is expanding to the low-risk population, because the detection rate for trisomy 21 surpasses that of traditional screening modalities. Although the sensitivity and specificity of cell-free DNA are superior to traditional screening, false-positive results do occur and may indicate an adverse maternal health condition, including maternal mosaicism or, rarely, malignancy. The risk of maternal cancer is significantly elevated when more than one aneuploidy is detected that is discordant from fetal karyotype. Given this risk as well as the rising incidence of cancer in pregnancy, patient counseling and malignancy evaluation should be considered in women when more than one aneuploidy is detected. We reviewed the published literature and developed an algorithm to evaluate women when these results are identified.