Aim: Nucleos(t) ide analogs have a risk for the development of Polymerase gene mutations and they can cause compensatory mutations in the HBV surface gene. Alteration in the `a determinant' of the s gene predispose for escape mutants. We aimed to evaluate primary, compensatory and escape mutations in chronic hepatitis B. Materials & methods: Two hundred nineteen specimens were obtained and HBV pol gene region was sequenced and amplified and HBV pol/s gene mutations were determined. Results: We detected primary mutation in 29.8% patients. Compensatory mutations were detected in 50.3% patients. Hepatitis B Immunoglobulin escape mutations, vaccine escape mutations, Hepatitis B diagnosis-escape and immunoselected amino acid substitutions were observed in 9.6%, 6.9%, 5.2% and 11.9% of patients, respectively. Antiviral drug-associated potential vaccine-escape mutants were detected in 17.9% patients. Conclusion: Therefore, epidemiological and demographical changes may be possible. Therefore, the typical HBsAg mutants and antiviral drug-associated potential vaccine-escape mutants should be monitored carefully.