Mycobacterium kansasii is a nontuberculous mycobacterium that causes pulmonary symptoms, commonly associated with underlying conditions, including malignancy, prior transplant, and HIV. However, rarely does Mycobacterium kansasii present with pleural effusion. We present a case of a 56-year-old female who presented with dyspnea and chest pain, and sputum culture was positive for acid-fast bacilli. A CT scan revealed a left-sided pleural effusion. Based on a thorough review of the literature using Embase and PubMed, we found that only 22 cases of a Mycobacterium kansasii pleural effusion have been reported. We provide a discussion on maintaining a broad differential in the treatment of immunocompromised individuals with Mycobacterium infection.