Purpose This report aims to promote awareness for opportunistic and atypical infections in the immunocompromised transplant population, as these may require highly specific treatments. This is the first described case of a patient with cytomegalovirus (CMV) tissue invasion presenting with a perianal fistula and abscess formation. Although CMV infection after transplant has been dramatically reduced in the modern, CMV syndrome with or without tissue invasive disease can still lead to significant morbidity and mortality. Therefore, it is important to maintain a high index of suspicion for CMV infection in transplant patients, for timely diagnosis and specific treatment. Methodology We conducted a literature review for CMV associated perianal disease and cutaneous disease in transplant patients and screened all available articles. We reported our case, and compared and contrasted each of these articles to our case. Results This is the first published case report of a patient with CMV tissue invasion presenting with a perianal fistula and abscess formation. The diagnosis and management of this case with a literature review is discussed. Conclusion We describe the first case of a perianal fistula with confirmed CMV inclusion bodies in a postoperative renal transplant patient. This highlights that a high index of suspicion for CMV pathology should be considered in this patient population for timely diagnosis and appropriate treatment. Furthermore, this report demonstrates the value of CMV prophylaxis in this group, which is especially important given the high morbidity and mortality associated with CMV infection in the immuno-compromised population and the specific management involved.