Semantic features, such as prototypical visual form or function, are often shared across multiple object concepts. How, then, are we able to resolve interference between object concepts that look alike but perform different functions (e.g., hairdryer and gun) or that do similar things but look rather dissimilar (e.g., hairdryer and comb)? We examined this issue in the current neuropsychological single-case study by asking whether perirhinal cortex (PRC) critically enables resolution of interference among object concepts at the level of their conceptually- and visually-based semantic features. We tested three patients with differing lesion profiles using a novel discrimination task involving stimuli for which visual and conceptual similarity were not linked across object concepts. We found that D.A., an individual with a brain lesion that includes PRC, was impaired at discriminating among object concepts when there was a high degree conceptual and visual semantic feature overlap among choices. We replicated this result in a second testing session. Conversely, patients with selective hippocampal or ventromedial prefrontal cortical lesions were unimpaired on this task. Importantly, D.A.’s performance was intact when (i) conceptual and visual interference among object concepts was minimized, and (ii) when the discriminations involved simple stimuli that did not require assessment of multiple stimulus dimensions. These results reveal a novel semantic deficit in a patient with PRC damage, suggesting that this structure represents object concepts in a manner that can be flexibly reshaped to emphasize task relevant semantic features.