Lesion studies in monkeys suggest that neocortical subregions of the medial temporal lobe (MTL) carry memory functions independent of the hippocampal formation. The present study investigates possible differential contributions of MTL subregions to spatial memory in humans. Eye movements toward remembered spatial cues (memory-guided saccades) with unpredictably varied memorization delays of up to 30 seconds were recorded in patients with postsurgical lesions of the right MTL, either restricted to the hippocampal formation (n = 3) or including the adjacent neocortex (n = 5) and in 10 controls. Although saccadic targeting errors of patients with selective hippocampal lesions did not differ from controls, saccadic targeting errors of patients with additional neocortical involvement showed a significant and contralaterally pronounced increase at memorization delays above 20 seconds. We conclude that the human medial temporal neocortex carries spatial memory functions independent of the hippocampal formation and distinct from spatial short-term memory.