Gallbladder cancer (GBC), while infrequent, is the predominant malignancy of the biliary tract. The absence of clinical symptoms in conjunction with aggressive behavior contributes to delayed diagnosis and unfavorable prognosis. This condition typically remains asymptomatic in its initial stages, making detection challenging. Herein, we report a case of adenosquamous carcinoma of the gallbladder in a 74-year-old Caucasian woman who was admitted due to anemia, gastrointestinal bleeding, and abdominal pain. Computed tomography (CT) of the abdomen demonstrated a formation adjacent to the neck of the gallbladder. A lesion with unclear boundaries in the IVb liver segment was also observed. CT-guided percutaneous biopsies were conducted on the thickened wall of the gallbladder and the suspicious area of the liver. The histological report from liver biopsy indicated carcinoma of the gallbladder characterized by squamous differentiation. Τhe case was discussed in an oncology board meeting, and the patient underwent exploratory laparotomy. Intraoperative observations revealed an invasive gallbladder neoplasm extending to the hepatoduodenal junction and the second part of the duodenum. The surgical team performed cholecystostomy and gastrojejunostomy with palliative intent. Gallbladder wall biopsies were obtained intraoperatively and histopathology results confirmed the initial diagnosis of adenosquamous carcinoma. The patient was referred to an oncology board meeting, and it was decided to be a combination of chemotherapy and chemoradiation according to the National Comprehensive Cancer Network (NCCN) guidelines.