Abstract Inflammatory liposarcoma is one of the rarest subtypes of well‐differentiated liposarcoma. We present an extremely rare case of well‐differentiated inflammatory liposarcoma that occurs in the muscularis of the gallbladder, which was difficult to diagnose before surgery due to the lack of specific clinical and imaging findings. Since cyclin‐dependent kinase 4 (CDK4) and murine double minute 2 (MDM2) both displayed amplification in this case, they are not only important markers for auxiliary diagnosis but also the focus of current targeted therapy.