This study provides a morphological characterization of the inner anatomy of the root canals of permanent first and second molars in Chalcolithic and early Bronze Age human fossils using cone-beam computed tomography. The general evolutionary trend in present-day human dentition is related to morphological simplification. As little is known about when this trend appeared in Homo sapiens populations, the aim of this work is to test the presence of modern radicular morphology 4,400 years ago. Fifty-four permanent first and second maxillary and mandibular molars of 17 individuals were included in the study. All maxillary first and second molars showed three separate roots. Almost all the lower molars analyzed (100% of first molars and 75% of second molars) had two separate roots. More differences in the canal system configuration were documented in the maxillary mesiobuccal roots than in the palatal or distobuccal roots. The most variable tooth in root and canal configuration is the maxillary second molar. It should be pointed out that 12.5% of the teeth analyzed showed a C-shaped root configuration. Anat Rec, 297:2342–2348, 2014. © 2014 Wiley Periodicals, Inc.