Cholestatic liver disease in children represents a diagnostic and therapeutic challenge. The requirement of a multidisciplinary approach, high levels of professional expertise, and the costs of genetic testing are a few of the reasons why such patients may suffer for want of an accurate diagnosis. Progressive familial intrahepatic cholestasis (PFIC) is a hereditary cholestatic liver disease, afflicted children often progressing to liver failure. Despite its potential to cause significant morbidity, it has seldom been studied in India. Preliminary observations made previously at our center while dealing with such cases have suggested that PFIC may actually not be as rare as described in Western literature. A lack of understanding of actual disease burden in India and no data on genotype-phenotype correlation compounds the issue. The aim of this review is to make pathologists aware of the nuances involved in understanding this disease and its diagnostic clues. As a specific diagnosis has direct therapeutic implication for this subset of patients, the onus is on the pathologist to ensure an accurate opinion. A PubMed-based literature search using the keywords "PFIC" and "progressive familial intrahepatic cholestasis" was done to analyze and disseminate both global and Indian work in this arena.