The goal was to study our experience in the management of a series of patients with a potentially curative subserosal gallbladder cancer who were prospectively treated by the authors. Between April 1988 and July 2004, 139 patients were enrolled in our prospective database. Of the above, 120 were operated on with an open procedure and the rest with laparoscopic surgery. In only eight patients was the diagnosis suspected before the cholecystectomy. The majority of tumors were adenocarcinoma. Six patients had an epidermoid tumor, and one had a carcinosarcoma. Of the patients, 74 underwent reoperation, while in 55 (70.2%) it was possible to perform an extended cholecystectomy with a curative aim. Operative mortality was 0%, and operative morbidity was 16%. Lymph node metastases were found in 10 (18.8%), while in 7 (13.2%) the liver was involved. The overall survival rate was 67.7%, while in those who underwent resection, the survival rate was 77%. Through the use of a multivariate analysis, the presence of lymph node metastasis was found to be an independent factor with respect to prognosis. The feasibility of performing an extended cholecystectomy in patients with gallbladder cancer and invasion of the subserosal layer allows for a good survival rate. The presence of lymph node metastases represents the main poor prognosis factor, and some type of adjuvant therapy should be studied in this particular group.