Introduction and importance:Azathioprine (AZA) used as an immunomodulator agent in the management of inflammatory bowel disease (IBD) increases the risk of the development of lymphoma.Case presentation:We present a case of a 45-year-old female receiving AZA for severe ulcerative colitis for 4 years. She presented with the chief complaints of bloody stool and abdominal pain for 1 month. Through a series of investigations including colonoscopy, contrast-enhanced computed tomography scan of the abdomen and pelvis, and biopsy with immunohistochemistry; she was diagnosed to have diffuse large B-cell lymphoma of the rectum. She is currently on a chemotherapeutic regimen and is planned for surgical resection after the completion of neoadjuvant therapy.Clinical discussion:AZA is classified as a carcinogen by the International Agency for Research on Cancer. Prolonged exposure to higher doses of AZA increases the risk of developing lymphoma in IBD. Previous meta-analysis and research indicate that the risk of development of lymphoma after the use of AZA in IBD increases by about four- to six-fold, especially in older age groups.Conclusions:AZA may increase the susceptibility to developing lymphoma in IBD, but the benefit far outweighs the risk. Precautions must be taken in prescribing AZA in older individuals which mandates periodic screening.