The purpose of this in vitro investigation was to compare in primary molars, the validity of DIAGNOdent™ 2095 on occlusal caries diagnosis used either separately or in combination with direct and/or indirect visual examinations, based on histological examination as the reference method. In 24 extracted primary molars, 111 occlusal pits were examined for caries by one trained operator (intra-examiner reliability k > 0.80), using the following examination methods: direct visual (DV), indirect visual (IDV), radiographic (XR), and fluorescence (DD) with the DIAGNOdent™. The extent of caries was then determined histologically. Sensitivity, specificity, accuracy, and the area under the ROC curve (AUC) were calculated for each method separately as well as for the combination of DD with DV and/or IDV. The DD accuracy was found both for lesions into enamel and into dentin to be 0.70 while the accuracy of the DD combination with DV and IDV was found to be 0.89. The DD AUC for lesions into enamel and into dentin, 0.68, were not statistically significant different from the other methods (p > 0.5), however the AUC of the combination of DD with DV and IDV, found to be 0.82, was higher than all the other methods, and this was statistically significant for enamel lesions. The validity of DIAGNOdent™ for occlusal caries diagnosis in primary molars was much higher when the DD was used in combination with direct and indirect visual examination, than when used by itself.