Objectiveproximal enamel caries lesions (PEC) are believed to initiate and progress to cavitation below the proximal contact area (PCA), but no evidence exists on the location of initial carious cavitation on the proximal surface with functional PCA. This study aimed to test the association of anatomical areas of the proximal surface with the severity of PEC and the frequency of cavitation in PEC in primary molars Designlaboratory, observational, transversal study. Exfoliated primary molars (n = 33) with functional PCA (biofilm-free PCA surrounded by biofilm) had their proximal surfaces (one/tooth) divided anatomically into up to nine areas: 3 areas based on the occlusal/cervical PCA boundaries (areas I, II, and III; occluso-cervically) and 3 areas based on the bucco/lingual PCA boundaries (A, B, and C), with area IIB representing the PCA and area IIIB as the sub-PCA (below the PCA). PEC (ICDAS scores 1 and 2–3) and cavitation in PEC were quantified in all areas using stereomicroscopy and microCT. PEC volume was quantified in areas IIB and IIIB under microCT ResultsPEC severity increased occluso-cervically. PCA and sub-PCA presented different PEC severities (higher in sub-PCA) and similar PCE volumes, but the odds of carious cavitation were much higher (Odds ratio = 197.4; 95 % CI: 8.7/4480.7) in the PCA than in the sub-PCA (no cavitation). ConclusionPCA presented lower PEC severity and similar PEC volume compared to sub-PCA, but PCA concentrated all cavitations in PEC, supporting a new model for the pathogenesis of PEC.