Background. It is unclear why cardiac myxomas develop. We describe a case of comorbid myxoma and chronic lymphocytic leukemia (CLL) to offer insights into the tumor's pathophysiology. Case. A 56-year-old female with recurrent venous thromboembolism developed embolic stroke. Transesophageal echocardiogram showed a 1.7 × 1 cm sessile left atrial mass at the interatrial septum. Histopathology revealed myxoma with a B cell lymphocytic infiltrate suggestive of a low grade lymphoproliferative disorder. Bone marrow biopsy and flow cytometry of blood and the cardiac infiltrate supported the diagnosis of atypical CLL. She was followed clinically in the absence of symptoms, organ infiltration, or cytopenia. After eighteen months, she developed cervical and axillary lymphadenopathy. Biopsy confirmed B cell CLL/small lymphocytic lymphoma. She elected to undergo chemotherapy with fludarabine, cyclophosphamide, and rituximab, with clinical remission. Conclusions. The coexistence of two neoplastic processes may be coincidental, but the cumulative likelihood is estimated at 0.002 per billion people per year. A shared pathogenic mechanism is more likely. Possibilities include chronic inflammation, vascular endothelial growth factor A, shared genetic mutations, changes in posttranslational regulation, or alterations in other cellular signaling pathways. Additional studies could expand our current understanding of the molecular biology of both myxomas and CLL.