Objective: Acromegaly associated to schizophrenia was first reported ~60 years ago, and so far, it is unclear whether this association is causal or not. Our aim was to report new cases with both clinical entities and to discuss the potential pathophysiological mechanisms of this association. Methods: Three new cases and data from literature are reviewed. Results: We report 2 males and 1 female diagnosed with schizophrenia and treated for several years with antipsychotics who developed acromegaly due to a growth hormone (GH)-secreting pituitary macroadenoma. In all cases, the diagnosis of schizophrenia preceded acromegaly with mean disease duration of ~12 years. Antipsychotic therapy was different in every patient. Two patients underwent transsphenoidal surgery. Histopathological study showed mixed GH- and prolactin-secreting adenoma in 1 patient and pure GH-secreting adenoma in the other patient. Several pathophysiological mechanisms related to alterations in dopaminergic neurotransmission due to psychiatric disease itself or its pharmacological treatment are proposed and discussed as likely linkage between schizophrenia and acromegaly. Conclusion: These case reports suggest that schizophrenia and/or its antipsychotic therapy in the long term might be in relation with the development of GH-secreting pituitary adenomas.