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Introduction Primary biliary cholangitis (PBC) is typically associated with elevated alkaline phosphatase (ALP). However, atypical forms with normal ALP levels may occur and are often underdiagnosed. Data on the clinical characteristics and treatment response of PBC with normal ALP are limited. This study aimed to describe the clinical, biological and histological features of patients with PBC and ALP ≤ 1.5× the upper limit of normal (ULN), and to identify predictors of response to ursodeoxycholic acid (UDCA).Methods We conducted a single-centre retrospective study including patients followed for PBC between 2016 and 2025. Patients were classified according to ALP level (≤ 1.5× ULN vs > 1.5× ULN). Diagnosis was based on cholestatic enzymes, liver biopsy findings and the presence of anti-mitochondrial M2 antibodies when available. Treatment response was assessed at 12 months using Paris II criteria. Multivariate analysis was performed to identify factors associated with complete biochemical response.Results A total of 106 patients were included, with a marked female predominance in both groups (>90%). Median age was 49 years in the ALP ≤ 1.5× ULN group and 46 years in the ALP > 1.5× ULN group. Anti-mitochondrial M2 antibodies were less frequently detected in patients with normal ALP compared with those with elevated ALP (44% vs 74%, p = 0.004). Patients with normal ALP more often had early-stage fibrosis (F0–F2) and typical histological features of PBC. Response to UDCA was significantly higher in the normal ALP group (68.9% vs 26.2%, p < 0.001). On multivariate analysis, ALP ≤ 1.5× ULN and mild to moderate fibrosis were independently associated with favorable treatment response.Conclusion PBC with normal ALP is an underrecognized entity associated with typical histological features and a higher likelihood of response to UDCA. Isolated elevation of gamma-glutamyl transferase in a suggestive clinical or immunological context should prompt consideration of early liver biopsy. These findings support proactive diagnostic strategies beyond classical ALP-based criteria.