•Lynch syndrome is an autosomal dominant disease characterized by a germline mutation in mismatch repair genes resulting in microsatellite instability and high mutational burden.•Lynch syndrome is responsible for 2% to 4% of all colorectal cancer cases and is associated with an up to 80% increase in the lifetime risk of colorectal cancer.•Thanks to better screening and earlier diagnosis, prognosis of patients with Lynch syndrome is improving, but also leading to the emergence of unusual presentations and histopathological variants.•Squamous cell colorectal carcinomas are extremely rare with only one previously reported case in association with Lynch syndrome.•There is lack of data regarding the best management for squamous cell cancers in the colon and rectum and treatment has been historically based on that for adenocarcinomas.•Evidence supporting the use of immunotherapy in mismatch repair deficient tumors is rapidly growing and has led to the first FDA molecular guided, tissue/site agnostic approval.•It can be argued that the management approach for patients with Lynch syndrome should be based on genetic and molecular factors regardless of tumor site or histology.