F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) has been used extensively to stage, restage, and follow neoplastic disease. However, focal accumulation of FDG may cause false-positive results in certain physiologic conditions. In this report, a unique PET and computed tomography (CT) combination scan helped define physiologic accumulation of FDG in the uterus during menstruation in a 40-year-old woman with a history of rectal melanoma and possible recurrent disease. An initial PET study, performed during menstruation, was followed immediately by a PET-CT scan, which showed marked accumulation of FDG in the posterior pelvis, localized to a retroverted uterus. An FDG PET-CT scan repeated 2 weeks later confirmed resolution of this "lesion." Thus, combined PET-CT correctly differentiated physiologic FDG uptake in a retroverted uterus from recurrent rectal melanoma. This case shows that physiologic FDG accumulation in the uterus should be considered when focal FDG accumulation is observed in the pelvis in women of reproductive age.