Background: Carcinoma of the gall bladder is a highly malignant tumor, with poor prognosis except when incidentally diagnosed at an early stage after cholecystectomy for illness other than carcinoma. The incidence of carcinoma of the gall bladder varies considerably in different parts of the world. A large number of risk factors have been proposed in the etiopathogenesis of carcinoma of the gallbladder. Cholelithiasis with or without chronic cholecystitis has been on the top among these causes. Objective: To study the expression of cyclin d1, p16 and retinoblastoma protein in carcinoma of the gall bladder. Method: This clinical study was conducted in the Department of Surgical Oncology, Institute of Medical Sciences, in collaboration with Department of Pathology, Banaras Hindu University, Varanasi. 60 patients of carcinoma gall bladder were included for the study who were further divided in three groups 25 in (study group), 25patients of cholelithiasis and 10 patients of normal gallbladder (control group). Result: In the present study a mean age of 47.4 ± 8.11 years (range: 25-70) was observed in patients of carcinoma of the gallbladder with 68% being in the 4th and 5th decade of life. Majority of patients were female 19 (76%) out of 25. The female to male ratio was 3.2:1 in present study. The common presenting symptoms in our study were pain in 88%, loss of appetite in 56.0%, loss of weight loss in 36%, abdominal lump 32.0% patients. The most common clinical sign in our study was tenderness in right hypochondrium (72.0 %), gallbladder lump in 36.0 % patients. Pallor was present in 28% cases, icterus in 12% cases and hepatomegaly in 12.0 %. We found strong positive relation between tumor metastasis and cyclinD1 expression (χ2 = 5.114, P Value =0.024; r = 0.452, P Value = 0.012). In our study Rb expression was present in 6(24%), 8(32%) and 5(50%) in carcinoma, chelelithiasis and normal gallbladder respectively. This difference is statistically not significant. (χ2 = 2.234, P Value = 0.327). Conclusion: There was a strong positive relation between metastatic tumors and cyclinD1 expression suggesting that aggressive malignancy of the gallbladder have higher cyclin D1 expression and its expression may act as a predictive biomarker for behaviour of the gallbladder malignancy.