Mesenteric or retroperitoneal actinomycosis is an extremely rare disease. The international databases have revealed only 10 cases affecting the mesenterium and another 52 cases affecting the retroperitoneum. We report a 78-year-old female who was admitted with complaints of abdominal pain. Laboratory examination revealed anemia and the clinical examination revealed an irregular mass in the abdomen. Ultrasound and computed tomography (CT) scans showed a solid mass in the mesenteric-retroperitoneal region. Biopsy of the nonresectable mass revealed the presence of chronic inflammation in the mesenteric area with Actinomyces colonies. The patient was treated with oral amoxicillin, 500 mg every 6 hours for 6 months. The symptoms disappeared, but the mesenteric-retroperitoneal mass remains, but smaller in size. Based on the review of the literature and the case reported here, we conclude that mesenteric-retroperitoneal actinomycosis is difficult to diagnose by means of noninvasive techniques as it can masquerade as a malignant process. An accurate diagnosis is always obtained in a histological or microbiological examination, often requiring surgical intervention. Treatment with penicillin has proven to be effective.