Carbohydrate antigen (CA) 125 is a glycoprotein produced by the serous epithelium, found to be increased in ovarian cancer and currently used in the follow-up of patients with this malignancy and to evaluate the response to therapy. However, an increase in the blood levels of this tumor marker has been recently reported even in patients with congestive heart failure. We report a case of a woman in whom previously high levels of CA 125 were related to the presence of an ovarian cancer; after bilateral oophorectomy and chemotherapy, the CA 125 levels remained within the normal range for several years, until a new increase was recently detected, raising the suspicion of a cancer recurrence. Clinical evaluation, together with comprehensive laboratory assessment, allowed us to exclude a malignancy and to identify the presence of congestive heart failure due to left ventricular systolic dysfunction as being responsible for the abnormal CA 125 levels. The patient's clinical improvement following medical therapy was associated with a reduction in the serum levels of CA 125 to normal values. The clinical relevance of this finding is discussed.