Background: P53 tumor-suppressor GENE which encodes a nuclear phosphoprotein that arrests cell cycle progress at G1, is one of the most frequently mutated GENEs in human cancers.Materials and Methods: In this study, 40 cases of Hodgkins disease (HD) which is the most common lymphoma in young adults, have been investigated for P53 GENE mutations. For each case, sections of paraffin-embedded tissue blocks were cut, a light hematoxylene stain was applied, and in order to enrich our samples for a higher percentage of Reed-Sternberg (RS) cells which are thought to be the neoplastic component of HD lesions, a microdissection technique was used. We used polymerase chain reaction (PCR) amplitication technique and single strand conformational polymorphism analysis (SSCP) to study mutations within exons 5 to 8 of GENE P53.Results: Six shifts were detected in five cases (12.5%), identified by SSCP (one shift in exon 5A, one in exon 5B, one in exon 6, two in exon 7 and one in exon 8). Conclusion: Since the specificity of PCR-SSCP is more than 95% for 100 to 300 bp polymerase chain reaction fragments, it is conceivable that P53 GENE mutation is not a common feature in HD. However, the samples with abnormal SSCP require nucleotide sequencing studies to assess whether the abnormal migration represents a mutation or a polymorphism.