Background: The purpose of this study was to examine the structure of dorsolateral, medial, and orbital regions of the frontal lobe in schizophrenia, and to determine whether their volumetric measurements were related to cognitive function and symptomatology. Methods: High resolution magnetic resonance imaging scans of the brains of 14 schizophrenic patients and 14 closely matched healthy controls were acquired. Volumes of gray and white matter of the left and right dorsolateral, medial, and orbital prefrontal brain regions were measured. Tests of verbal and visual memory and executive functions were used to assess cognitive function. The SANS and SAPS were used to obtain symptom ratings in patients. Results: Data of 13 schizophrenic patients were analyzed. Patients showed a general, though not significant, decrease in volumes of frontal regions as compared to controls. In patients, but not in controls, smaller left and right prefrontal gray matter volumes were significantly correlated with impaired performance on immediate recall in verbal and visual memory and semantic fluency. Furthermore, in patients, smaller total orbitofrontal gray matter volume was significantly correlated with more severe negative symptomatology (r(s) = -. 76, p = .006). Conclusions: These findings suggest that in schizophrenia, deficits in verbal and visual memory and semantic fluency and negative symptoms may be related to (subtle) abnormalities in frontal lobe structure.