The intracystic electrolyte content is generally used to identify different breast cyst subpopulations: cysts containing high K+ levels have been associated with an increased risk of subsequent breast cancer. In order to define whether other biochemical features of breast cyst fluid (BCF) might further explain such an increased risk, we determined the content of epidermal growth factor (EGF), a known mitogenic factor for normal and transformed breast epithelium, in cysts of women with breast cancer or proliferative lesions of the breast (atypical ductal or lobular hyperplasia and proliferative disease without atypia). Median intracystic EGF levels were significantly higher in patients with breast cancer or atypical hyperplasia than in cysts of women without any clinical or instrumental evidence of proliferative disease chosen as controls (p < 0.05 and p < 0.01, respectively). In patients affected by proliferative disease without atypia, intracystic EGF levels were not different either from controls or from the other study groups. No significant difference among groups was observed in the prevalence of Na+/K+ < 3 cysts, this being the most frequently observed type of cysts in all groups except in that with proliferative disease without atypia. No significant difference in EGF levels between cysts ipsilateral or contralateral to the biopsy was observed within each histological group. Our results indicate that EGF levels are higher in cysts aspirated from breasts with an associated proliferative pathology, either benign or neoplastic. The determination of intracystic EGF, combined with that of electrolyte content, might help to identify a subset of patients with gross cystic disease of the breast at potentially higher risk of developing breast cancer.