Background. Differentiating between schizophrenia and major depression with psychotic features often reveals diagnostic dilemma. Both share psychotic features and severe impairment in occupational functions. Severe psychomotor retardation, not uncommon in psychotic depression, may simulate negative symptoms of schizophrenia. Our work aims at utilizing Wisconsin Card Sorting Test (WCST) performance as a potential differentiating neurocognitive tool. Subjects and Methods. 60 patients were recruited randomly from the outpatient service at Alexandria University Hospital: 30 patients with schizophrenia and 30 patients with chronic psychotic depression. They were subjected to Clinical Global Impression for Severity (CGI-S) scale and Wisconsin Card Sorting Test (WCST) 128 card computerized version. Results. Both groups were balanced in terms of gender distribution, severity and duration of illness. The study compared all parameters of WCST. Only perseverative errors showed mild significant difference (P < 0.05) that disappeared when applying Bonferroni adaptation, setting significance level at 0.01 instead of 0.05. Conclusion. Performance on WCST is similar in schizophrenia and severe depression with psychotic features in most of the measured parameters and hence could not serve as a supplementary tool differentiating between both diagnoses in our study.