Inactivation of the p53 tumor suppressor gene is considered to occur as a late event involved in hepatocarcinogenesis. Its detection is thought to provide a useful information for the clinical management of hepatocellular carcinomas (HCCs). A rapid screening test was devised for allelic loss of the p53 gene in samples obtained by needle biopsy using non-radioisotopic (RI) microsatellite analysis combined with the microdissection method for clinical laboratory. Biopsy materials from 23 HCCs were examined to detect loss of heterozygosity (LOH) of the p53 gene after use for a histopathological diagnosis. Two microsatellite loci in the p53 gene were amplified by the polymerase chain reaction (PCR) using DNA extracted from microdissected cells, and amplified DNA fragments were subjected to non-RI detection using silver staining. More than 40-50 microdissected cells from a formalin-fixed paraffin-embedded tissue are enough to amplify both alleles of the p53 gene during the PCR. The combination of the two polymorphic microsatellite markers encompassed 60% of Japanese patients as informative. This method has detected LOH of the p53 locus in 54% of informative primary HCCs. Furthermore, LOH of the p53 gene was frequently detected in more advanced HCC as to the histological grade and clinical stage as shown in the previous report. The system for rapid and safe detection of the p53 gene allelic loss should provide useful information on the strategy for the treatment of HCC in the clinical laboratory.