18F-FDG PET/CT is a useful modality for identifying high-glucose-consuming cells, such as cancer cells by the glucose metabolism of FDG. FDG is taken up by cancer and inflammatory cells but occasionally, there is some FDG uptake on normal tissues as a result of their individual physiological characteristics. In particular, in fertile females, unusual FDG uptake in the breast changes according to the stages in the menstrual cycle, which can adversely affect a diagnosis. Therefore, this study examined the change in breast FDG uptake in the menstrual cycle on 18F-FDG PET/CT. One hundred and sixty females (34 ± 3.5 years old), who had not undergone a gynecologic anamnesis and had a regular menstrual cycle over the previous 6 months, were examined from March 2011 to February 2012. The subjects were divided into the following 4 groups (each with 40 patients): flow phase, proliferative phase, ovulatory phase and secretory phase using Pregnancy Calculator 0.14 and history taking. Discovery STE (GE Healthcare, USA) was used as the PET/CT. The SUVs on the accumulated region on the breast were analyzed, and 3 nuclear medicine specialists performed a blind test. The SUVs on the breast were the flow phase (1.64 ± 0.25), proliferative phase (0.93 ± 0.28), ovulatory phase (1.66 ± 0.26) and secretory phase (1.77 ± 0.28). Higher uptake values were observed in the secretory, flow phase and ovulatory phase (p< 0.05). The accumulation of the breast was divided into the following 3 grades compared to the lung and liver by gross analysis: the breast uptake was equal to the lung (Grade I); between the lung and liver (Grade II); and equal to or greater than the liver (Grade III). These results showed a high uptake value in the secretory, flow phase and ovulatory phase (p <0.05). In fertile females, the FDG uptake of the breast showed changes according to the menstrual cycle, which can be used to improve the diagnosis of breast disease. Therefore, the false-negative findings of breast disease can be reduced by performing an examination at the appropriate period through history taking and considering the individual menstrual cycle.