The role of c-erbB-2 protooncogene status in feline invasive mammary carcinomas (FMCs) was assessed through the HER-2 receptor immunohistochemical expression. The HER-2 overexpression was then correlated with some relevant histologic parameters and with the clinical course of the disease during a 2-year follow-up. Forty-seven FMCs from surgically treated queens were considered. Tumors were classified according to the WHO criteria and stromal or lymphatic invasion (or both) and histologic grading were recorded. The immunohistochemical staining was performed on paraffin sections and a well-defined scoring system based upon numbers of HER-2 receptors expressed on the cell surface was applied according to standard guidelines. Overall survival (OS) distributions were generated with the Kaplan-Meier method. HER-2 overexpression was detected in 28 of the 47 carcinomas (59.6%). This parameter was demonstrated to be significantly correlated with the shorter OS ( P = 0.02). However, the HER-2 overexpression did not show significant correlation with histologic type, tumor grading, or presence of lymphatic invasion. Furthermore, the HER-2 overexpression appeared with a higher percentage in FMCs than what is reported in canine or human mammary carcinomas. The significant correlation with a shorter OS suggests a possible role of HER-2 as an additional marker of malignancy in FMCs and as a reliable prognostic indicator As in the human oncology practice, the identification of the FMCs that overexpress HER-2 may also promote new therapeutic strategies.