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This study presents a description and comparative analysis of Middle Pleistocene permanent and deciduous teeth from the site of Qesem Cave (Israel). All of the human fossils are assigned to the Acheulo-Yabrudian Cultural Complex (AYCC) of the late Lower Paleolithic. The Middle Pleistocene age of the Qesem teeth (400–200 ka) places them chronologically earlier than the bulk of fossil hominin specimens previously known from southwest Asia. Three permanent mandibular teeth (C1-P4) were found in close proximity in the lower part of the stratigraphic sequence. The small metric dimensions of the crowns indicate a considerable degree of dental reduction although the roots are long and robust. In contrast, three isolated permanent maxillary teeth (I2, C1, and M3) and two isolated deciduous teeth that were found within the upper part of the sequence are much larger and show some plesiomorphous traits similar to those of the Skhul/Qafzeh specimens. Although none of the Qesem teeth shows a suite of Neanderthal characters, a few traits may suggest some affinities with members of the Neanderthal evolutionary lineage. However, the balance of the evidence suggests a closer similarity with the Skhul/Qafzeh dental material, although many of these resemblances likely represent plesiomorphous features.