Lamivudine resistance is a result of mutations in YMDD motif in which rt203-206th codons (Y: tyrosine; M: methionin; D: aspartic acid; D: aspartic acid) of reverse trancriptase; the catalytic part of hepatitis B polymerase enzyme, takes place. In this study we aimed to show the YMDD motif variants in chronic hepatitis B patients who have presumably developed lamivudine resistance due to viral polymerase gene mutation during lamivudine therapy. Twenty lamivudine treated patients were included in the study, and HBV-DNA was extracted from the sera of the patients by using extraction kit (Invisorb, Instant Spin DNA/RNA Virus Mini Kit, Germany). A line probe assay (INNO-LIPA HBV DR; INNOGENETICS N.V, Ghent, Belgium) was used to determine YMDD motif variants at viral polymerase gene fragment in HBV-DNA samples of these patients and evaluated colorimetrically. In 12 (60%) patients' samples YMDD motif variants were detected leading to lamivudin resistance. Eleven (91.6%) of the 12 samples having motif variants were YMDD variant and wild-type combination. While YMDD + YIDD combination was determined in only one specimen, YMDD + YVDD combination was determined in six. Mixed combination of YMDD + YVDD + YIDD were detected in four samples. In 8 (66.6%) HBV-DNA samples YMDD variants were accompanied with L180M variants. It can be concluded that determination of genotypic resistance before the expression of phenotypic resistance during lamivudin therapy is important since addition of adefovir to the therapy at an early stage will prevent the occurence of hepatitis with mutant species. Thus lamivudin resistance should be followed up regularly in all of the chronic hepatitis B patients under lamivudin therapy.