Recently, neuroimaging and patient-lesion methods have been combined to explain anomalies such as patients’ intact performance on tasks on which they would be predicted to perform poorly. In some cases, preserved performance has been attributed to activation of residual tissue within the damaged region. However, activation of remnant tissue can also occur in relation to impaired performance and, thus, may not necessarily correspond to successful recruitment. To constrain these neuroimaging interpretations, what is needed is a paradigm with closely matched conditions that yields intact and impaired performance in the same patient. We investigated this in H.C., an amnesic person with congenital abnormalities of the hippocampus and its connections, who was scanned during remembering and imagining, abilities known to depend on the hippocampus. Specifically, we examined whether differences in activation and/or functional connectivity would explain H.C.’s compromised ability to construct events relating to herself in autobiographical memory (SELF condition) and events relating to personally familiar others (FAMILIAR condition) versus her intact ability to construct events relating to unknown others (UNFAMILIAR condition). Despite behavioral dissociations in H.C., the pattern of activation and functional connectivity supporting her performance was strikingly similar to that of controls across conditions. Most notably, like controls, H.C. showed robust hippocampal activation and functional connectivity to the hippocampus, both when her performance was intact and impaired. Across all conditions, H.C. activated several extra-hippocampal regions to a greater extent than did controls, and modest differences were observed in functional connectivity between extra-hippocampal regions. Taken together, these findings urge caution when drawing conclusions about the functional integrity of a structurally compromised brain region even when it is activated and/or co-activated with other regions.