Background and Aim: Gallbladder (GB) cancer has poor prognosis as it progresses very fast. Etiology or pathogenesis of GB cancer is still obscure and very little is known about it. A better understanding of risk factors that lead to its development could help improve the management options. Presence of stones in GB generates varied mucosal reaction which results in different types of histopathological changes. Our aim was to correlate the various types of mucosal response like inflammation, hyperplasia, metaplasia, and carcinoma to different gall stones characteristics (like number and morphology type). Materials and Methods: A retrospective study of 346 cases of removed GB was done which was based on the histological changes. A total of 313 (90%) were associated with gallstones and the rest 33 cases (10%) were of acalculous cholecystitis. The changes in mucosa of calculous GB (313 cases) were studied and correlation between the mucosal changes and the number and type of stones was evaluated. Varied parameters of gall stones like number and morphological type were studied. Tissue section for histopathological studies was taken from fundus, body, neck, and from abnormal looking areas while doing grossing. Results: Gender study revealed a higher incidence of inflammatory changes in males, while GB hyperplasia, intestinal metaplasia, and cancer were only found in females. A progressive increase in the average age was noticed fromintestinal metaplasia to carcinoma, suggesting that the metaplasia-carcinoma succession may occur in GB cancer. Conclusion: Correlation of mucosal changes with size and morphological type of stones has suggested that there could be an association between some histological alterations of GB and cancer.