Gliomas are characterized by highly variable biological behavior. After surgical resection and postoperative therapy they frequently recur with the same or higher-grade histology. Although a number of genetic aberrations have been described in gliomas of different histological types, the molecular mechanisms of the histological and clinical progression are poorly understood. In this study, we performed longitudinal microsatellite and mismatch repair gene analysis in paired samples of primary and recurrent gliomas in order to reveal whether genetic instability is associated with tumor progression. The 7 microsatellite loci of the 7 patients displayed a total of 18 (54.5%) alterations in the primary and 15 (45.5%) alterations in the recurrent gliomas as compared with the corresponding non-neoplastic cells, but no alterations were found in the hMLH1 and hMSH2 genes. These results suggest that microsatellite instability is associated with the development of the primary gliomas rather than with the recurrence or progression, and it is not associated with structural alterations in the hMLH1 or hMSH2 genes. Comparison of the microsatellite patterns in primary and secondary gliomas revealed 4 different modalities of clonal evolution, involving clonal identity, clonal deletion, clonal progression, and different clonality, suggesting that intensive clonal selection may play a central part in the recurrence of gliomas.