This study aimed to evaluate in vitro performance of near-infrared laser transillumination (NIR-LTI) for detecting early occlusal caries in permanent teeth and compare it with quantitative light-induced fluorescence (QLF), DIAGNOdent Pen (DDPen), and conventional radiography (CR). Ninety-four occlusal surfaces presenting International Caries Detection and Assessment System (ICDAS) scores ranging from 0 to 3 were selected. For the NIR-LTI examination, images were captured using a prototype, which consists of a laser beam (808 nm) and an infrared CCD camera. One occlusal site on each tooth was assessed twice by two examiners. The teeth were prepared histologically and assessed for the presence of early caries. The intraexaminer correlation showed no difference between the NIR-LTI, DDPen, and QLF analytical methods, but all these methods differed from CR. Interexaminer reproducibility was moderate for NIR-LTI, which showed sensitivity (0.68), specificity (0.85), accuracy (0.73), and area under the receiver-operating characteristic (ROC) curve (0.76) similar to those of the fluorescence method and different from those of the CR. In conclusion, the performance of NIR-LTI was comparable to that of DDPen and QLF and may therefore be considered a valid and reliable alternative for the diagnosis of incipient lesions on the occlusal surface of permanent teeth.