BACKGROUND Hepatitis B virus (HBV) precore (PC) and basal core promoter (BCP) variants are well known; however, their prevalence in North America is unclear, especially among hepatitis B e antigen-negative patients. OBJECTIVE To investigate the prevalence of PC⁄BCP mutations and their clinical significance. METHODS One hundred twenty-eight patients positive for both hepatitis B surface antigen and hepatitis B e antibody were selected, and PC⁄BCP mutations were identified using a line probe assay. The subjects' charts were reviewed for race⁄ethnicity, HBV genotype, HBV viral load, sex, liver enzyme levels, imaging and biopsy results up to 10 years before the study. RESULTS The prevalence of PC and BCP variants were 47.6% and 62.5%, respectively. Older age was associated with aspartate aminotransferase-to-platelet index ratio (APRI) ≥0.7 (P=0.011) and abnormal imaging⁄biopsy results (P=0.0008). Although the presence of BCP variant(s) was associated with APRI ≥0.7 (P=0.029), it was not associated with abnormal imaging⁄biopsy results. The combination of age ≥50 years and the presence of BCP variant(s) was associated with abnormal imaging⁄biopsy results, suggestive of either cirrhosis or hepatocellular carcinoma (not observed with PC mutation). Neither sex or genotype, or median HBV viral load showed significant influence on any of these outcomes. CONCLUSIONS The present study suggests that the prevalence of PC and BCP mutations are higher than what has been previously reported. One potential explanation would be increased immigration in the past decade. Considering the potential public health and clinical implications of these variants, long-term multicentre and prospective studies could further unravel the uncertainty around these variants.