This study examined the impact of seizure-related items and selected comorbid medical conditions on Minnesota Multiphasic Personality Inventory, Second Edition (MMPI-2), Scales 1 and 3 and the psychogenic nonepileptic seizure (PNES) profile [Wilkus RJ, Dodrill CB, Thompson PM. Intensive EEG monitoring and psychological studies of patients with pseudoepileptic seizures. Epilepsia 1984;25:100–7] in patients with epileptic seizures (ES) and PNES. Sixty patients with a long-term video/EEG monitoring diagnosis of either ES (N =30) or PNES (N =30) and valid MMPI-2 profiles were included in this study. MMPI-2 seizure-related items [Derry PA, Harnadeck MCS, McLachlan RS, Sontrop J. Influence of seizure content on interpreting psychopathology on the MMPI-2 in patients with epilepsy. J Clin Exp Neuropsychol 1997;19:396–404] were removed to determine if their inclusion overpathologizes and/or misclassifies patients with epilepsy. Removal of seizure-related items did not result in any clinically meaningful changes in MMPI-2 profiles for patients with ES. The presence of comorbid medical conditions was not associated with greater Scale 1 or 3 scores or the likelihood of a PNES profile in either group. Results suggest that clinical elevations on MMPI-2 profiles may not be explained by the presence of seizures or comorbid medical conditions.