<p>Porcelain gallbladder (PG), characterized radiographically by gallbladder wall calcification, is a rare condition with significant clinical importance due to its association with gallbladder cancer (5–22%). This review explores the epidemiology, pathophysiology, and molecular mechanisms of PG development. Strong correlation with gallstones (&gt; 60%) establishes cholelithiasis as the primary risk factor, with female sex, advanced age, and metabolic disorders also contributing significantly. The pathogenesis involves sustained inflammation, leading to fibrosis, scarring, and ultimately calcium deposition. At the molecular level, pro-inflammatory cytokines, macrophage activation, and fibroblast differentiation ultimately result in collagen deposition and calcification. Estrogen contributes to female predominance through reduced gallbladder motility and increased cholesterol secretion via ESR1, ESR2, and GPER1 receptors. Postmenopausal women remain at risk despite lower estrogen levels due to antioxidant system changes and structural alterations from previous pregnancies. Emerging evidence suggests roles for Helicobacter pylori and other urease-producing bacteria in PG development. The relationship between calcification patterns and malignancy remains controversial, with incomplete calcification potentially carrying higher cancer risk. This review synthesizes current knowledge while highlighting areas requiring further investigation. Evaluation of the urinary bladder for calcification and malignancy is advised when PG is detected, to explore potential associations for future research.</p>