Cowden syndrome is an uncommon autosomal dominant disorder characterized by multiple hamartomas in various tissues. It is associated with germline mutation in the phosphatase and tensin homolog (PTEN) gene. It has an increased risk of malignancies of various organs (commonly breast, thyroid, and endometrium) and benign overgrowth of tissues like skin, colon, and thyroid. Here, we present a case of Cowden syndrome in a middle-aged female who presented with acute cholecystitis with gall bladder polyps along with intestinal polyps. She underwent total proctocolectomy with ileal pouch-anal anastomosis (IPAA) with diversion ileostomy and cholecystectomy, which was further proceeded to completion of radical cholecystectomy based on the final histopathology report as incidental gall bladder carcinoma. To the best of our knowledge, this association is seen for the first time in the literature. In Cowden syndrome, patients should be counseled for regular follow-up and instructed to be aware of the signs and symptoms of different types of cancers with higher incidence.