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Abstract Investigations into how individual neurons encode behavioral variables of interest have revealed specific representations in single neurons, such as place and object cells, as well as a wide range of cells with conjunctive encodings or mixed selectivity. However, as most experiments examine neural activity within individual tasks, it is currently unclear if and how neural representations change across different task contexts. Within this discussion, the medial temporal lobe is particularly salient, as it is known to be important for multiple behaviors including spatial navigation and memory, however the relationship between these functions is currently unclear. Here, to investigate how representations in single neurons vary across different task contexts in the medial temporal lobe, we collected and analyzed single‐neuron activity from human participants as they completed a paired‐task session consisting of a passive‐viewing visual working memory and a spatial navigation and memory task. Five patients contributed 22 paired‐task sessions, which were spike sorted together to allow for the same putative single neurons to be compared between the different tasks. Within each task, we replicated concept‐related activations in the working memory task, as well as target‐location and serial‐position responsive cells in the navigation task. When comparing neuronal activity between tasks, we first established that a significant number of neurons maintained the same kind of representation, responding to stimuli presentations across tasks. Further, we found cells that changed the nature of their representation across tasks, including a significant number of cells that were stimulus responsive in the working memory task that responded to serial position in the spatial task. Overall, our results support a flexible encoding of multiple, distinct aspects of different tasks by single neurons in the human medial temporal lobe, whereby some individual neurons change the nature of their feature coding between task contexts.