Clinicopathologic features of 31 patients with subclinical gallbladder carcinoma were reviewed in an attempt to determine the parameters for a course of therapy. Subclinical gallbladder carcinoma was defined as a gallbladder carcinoma that was first diagnosed microscopically by surgical pathologists. Of 31 patients, there were 26 women and 5 men, ranging in age from 54 to 84 years (mean age: 68 years). All 31 patients had undergone cholecystectomy for presumed benign gallbladder conditions. The 31 gallbladder carcinomas consisted of 6 carcinomas limited to the mucosa or the muscle coat (m or pm) and 25 carcinomas extending into the subserosal layer with surgical margins free of malignant cells in 14 (ss ew [-]) and affected by malignant cells in 11 (ss ew [+]). Cumulative 1-year, 3-year, and 5-year survival rates of six patients with m or pm carcinoma were 100% (p less than 0.001, versus ss ew [+] at 1 year), 100% (p less than 0.05, versus ss ew [-] at 3 years), and 100% (p less than 0.05, versus ss ew [-] at 5 years) compared with 91% (p less than 0.01, versus ss ew [+] at 1 year), 65%, and 65% of 14 with ss ew (-) carcinoma and 43%, 0%, and 0% of 11 with ss ew (+) carcinoma. Thirteen of the 31 patients died of local recurrence and/or liver metastasis. Univariate logrank analysis of 10 prognostic factors showed that depth of invasion, venous invasion, and surgical margin were prognostic factors. Multivariate Cox-regression analysis of these three profound factors demonstrated that surgical margin and depth of invasion were independent variables. These results showed that m or pm subclinical gallbladder carcinoma does not necessarily require an additional operation, whereas ss ew (-) and ss ew (+) carcinomas necessitate additional resection and adjuvant treatment.