Background/aims: Hepatitis B virus infection is an epidemiological problem throughout the world, including in Turkey. Lamivudine is one of the hepatitis B virus reverse-transcriptase inhibitors used for the treatment of chronic hepatitis B virus infection. Lamivudine resistance can develop not only following treatment; it can also be seen in untreated patients. This resistance is related with structural changes in the tyrosine-methionine-aspartate-aspartate motif of the polymerase enzyme gene. Our objective was to evaluate the prevalence of lamivudine resistance in Turkish chronic hepatitis B virus-infected patients with D genotype before antiviral treatment. Methods: Seventy-seven patients with chronic hepatitis B virus infection were evaluated for viral loads, HBeAg, anti-HBe antibody, ALT levels, histological activity index, and tyrosine-methionine-aspartate-aspartate mutations. Results: Tyrosine-methionine-aspartate-aspartate motif mutations were determined in 3 of 24 HBeAg positive and 3 of 53 anti-HBe positive patients with a rate of 7.8%. Two of the mutations were YIDD and 4 were YVDD. Median ALT value in patients with mutations was 88 IU/L (range 55-276) and histological activity index was 9 (range 6-10); these values in patients without mutations were 58 (range 19176) and 10 (range 2-18), respectively. Knodell fibrosis scores of patients were as follows: 0: 13.2%, 1:28.9%, 2:21.1%, 3:34.2%, and 4:2.6%. There were no significant differences between the patients regarding Knodell fibrosis scores. One patient was diagnosed as cirrhosis. Conclusions: Evaluation of chronic hepatitis B virus patients for lamivudine resistance and planning the treatment accordingly may prevent complications and can increase the effectiveness of the treatment.