Background: c-Myc protooncogenes have been implicated in the tumourigenesis of extracerebral lymphomas, however only afew studies on this oncogenic molecule have been available for primary central nervous system lymphoma (PCNSL)., Objective: To determine the prevalence ofprotein overexpression and gene amplification of c-Myc in PCNSL and to correlate with histological and immunophenotypic subtypes of malignant lymphoma according to WHO classification of tumors of haematopoietic and lymphoid tissue 2001., Setting: King Chulalongkorn Memorial Hospital, Thailand., Design: Descriptive study., Material: 25 Thai patients presented between 2001 and 2005., Method: The overexpression and amplification of c-Myc in malignant lymphoma were studied by means of immunohistochemistry and chromogenic in situ hybridization (CISH), respectively, in formalin-fixed, paraffin-embedded specimens. The histomorphology and immunohistochemistry were used to subclassify PCNSLs according to WHO classification 2001., Results: Fourteen males and eleven females were recruited. They were between the ages of 21 and 86 years with the mean of 53 years. Eight had documented human immune deficiency virus (HIV) infection. Four of 17 immunocompetent cases overexpressed c-Myc protein without c-Myc gene amplification. No immunocompromised cases showed overexpression of c-Myc protein. All PCNSLs were classified as diffuse large B-cell lymphoma., Conclusion: In PCNSL, c-Myc overexpression is notfound immunocompromised (HIV-infected) patients and is found in 23.5% of the immunocompetent individuals without c-Myc gene amplification. All PCNSLs are diffuse large B-cell lymphoma according to WHO classification 2001.