Dental caries is a ubiquitous disease affecting all age groups and segments of the population. It is known that not all caries lesions progress to cavitation, but little is known regarding the progression pattern of caries lesions. This study's purpose was to evaluate the natural history of dental caries using a standardized, visually based system, the International Caries Detection and Assessment System (ICDAS). The study population consisted of 565 consenting children, who were enrolled and examined at baseline and at regular intervals over 48 months with ICDAS and yearly bitewing radiographs. Of these, 338 children completed all examinations. Not all lesions cavitated at the same rate, differing by surface type and baseline ICDAS severity score and activity status. With increasing severity, the percentage of lesions progressing to cavitation increased: 19%, 32%, 68%, and 66% for ICDAS scores 1, 2, 3, and 4, respectively. Lesions on occlusal surfaces were more likely to cavitate, followed by buccal pits, lingual grooves, proximal surfaces, and buccal and lingual surfaces. Cavitation was more likely on molars, followed by pre-molars and anterior teeth. Predictors of cavitation included age, gender, surfaces and tooth types, and ICDAS severity/activity at baseline. In conclusion, characterization of lesion severity with ICDAS can be a strong predictor of lesion progression to cavitation.