OBJECTIVE: We investigated the clinicopathological characteristics and immunophenotype of female genital system diffuse large B-cell lymphoma (DLBCL) in order to improve diagnosis and therapy efficacy. PATIENTS AND METHODS: The clinicopathologic features of 13 cases with primary DLBCL of the female genital system were studied retrospectively. According to the immunophenotypes, 10 cases were classified as germinal center B-cell-like DLBCL and the other 3 as non-center B-cell-like DLBCL. RESULTS: The immunohistochemistry data showed that CD20, PAX-5, and CD79a tested positive, while CD3, CD43 and CD45RO tested negative in all 13 cases. In 7 cases EMA was positive, in 9 cases CD10 was positive, in 11 cases bcl-6 was positive, and in 9 cases MUM-1 was tested positive. In one case, the Ki-67 index was less than 59%, in 3 cases Ki-67 index was between 60% to 89% and it was more than 90% in the remaining 9 cases (the median was 90%). All 13 patients underwent hysterectomy, while in 10 of them hysterectomy was followed by chemotherapy. The survival time was 3 to 20 months. CONCLUSIONS: Primary diffuse large B-cell lymphoma of the primary female genital system is a rare and highly invasive condition that can be easily misdiagnosed. A complete diagnosis is very important because the treatment and prognosis vary in different histological types. Moreover, the immunohistochemistry is an useful diagnostic method for this type of cancer.