BACKGROUND The prognosis of thymoma is related mainly to the tumor stage. The prognostic value of argyrophilic nucleolar organizer regions (AgNORs) has been demonstrated in several human neoplasias. Ninety primary thymomas were investigated retrospectively to assess whether AgNOR analysis could offer additional prognostic information. METHODS Sections from surgically resected thymomas, routinely fixed in formol and embedded in paraffin, were stained with the argyrophilic method of Ploton. The mean number of AgNORs in the nuclei of 100 tumor cells (AgNOR counts) was calculated for each case. The association between AgNOR counts and survival was assessed by means of uni- and multivariate survival analyses. RESULTS On univariate analysis, AgNOR counts were associated significantly with 5- and 10-year survival rates (95% and 90%, respectively, for thymomas with 5.58 or fewer AgNORs per cell, but only 55% and 44%, respectively, for tumors with more than 5.58 AgNORs per cell; P < 0.0001). Histologic subtypes of the American classification (P = 0.0006) and clinical stage (P < 0.0001) also were correlated with prognosis. The multivariate survival analysis showed that AgNOR counts (P = 0.001), clinical stage (P < 0.001), and age (P = 0.011) were independent prognostic variables. AgNOR counts were associated with histologic subtypes in the American (P = 0.0001) and European (P = 0.005) classifications and with the clinical stage (P < 0.0001). Moreover, thymoma cells and intermingling lymphocytes showed different numbers of AgNORs and patterns of AgNOR distribution. CONCLUSIONS Analysis of argyrophilic nucleolar organizer regions provides useful prognostic information for patients with thymomas and offers an exact evaluation of the proliferative activity of the neoplastic cells even for thymomas with prominent lymphocytic infiltration.