Tests of executive abilities, such as discrimination reversal and attentional set shifting, are sensitive to prefrontal cortex (PFC) damage in primates. The purpose of the present study was to use a primate reversal task to determine if PFC in the mouse is involved in similar cognitive functions. Mice with lesions of medial PFC and Sham operated control animals were trained on a series of visual problems in a computer-automated touchscreen apparatus using stimuli that varied in either pattern (lines) or luminance (black-white). PFC-lesioned mice learned to discriminate both sets of stimuli as readily as controls, but displayed a stimulus specific (pattern only) deficit on the reversal task. Analysis of error patterns on the line reversal suggests the deficit exhibited by PFC-lesioned mice was related to stimulus specific aspects of visual attention, rather than perseveration. These results demonstrate that medial PFC may play a role in control of directed attention and provide further evidence that the touchscreen procedure can be a useful tool for examining functional similarities in brain regions of very diverse species.