Unlike vision or audition, human olfaction is generally considered evolutionarily ancient and well-functioning at birth, yet there have been few empirical data on the development of olfactory acuity. The current study has assessed olfactory discriminability in children aged 3 to 6 years with 16 pairs of single-compound odorants that differ in various degrees in structure and smell. We report a significant improvement over age in young children’s overall olfactory discriminability. Critically, such improvement is modulated by the degree of structural similarity between odorants independent of odor familiarity. Our findings indicate that odor representations in the olfactory system are fine-tuned during early childhood (3–6 years of age) to allow refined discrimination. Moreover, they suggest the need to take molecular similarity into consideration in the evaluation of olfactory discrimination in pediatric populations.