Non-intrusive, non-contacting frequency-domain photothermal radiometry (FD-PTR or PTR) and frequency-domain luminescence (FD-LUM or LUM) have been used with 659-nm and 830-nm laser sources to detect artificial and natural sub-surface defects in human teeth. Fifty-two human teeth were examined with simultaneous measurements of PTR and LUM with the 659-nm laser and compared to conventional diagnostic methods including continuous (dc) luminescence (DIAGNOdent), visual inspection and radiographs. To compare each method, sensitivities and specificities were calculated by using histological observations as the gold standard. With the combined criteria of four PTR and LUM signals (two amplitudes and two phases), it was found that the sensitivity of this method was much higher than any of the other methods used in this study, whereas the specificity was comparable to that of dc luminescence diagnostics. Therefore, PTR and LUM, as a combined technique, has the potential to be a reliable tool to diagnose early pit and fissure caries and could provide detailed information about deep lesions with its depth profilometric character. Also, from the experiments with the teeth having natural or aritficial defect, some depth profilometric characteristics were confirmed. The major findings are (i) PTR is sensitive to very deep (>5 mm) defects at low modulation frequencies (5 Hz). Both PTR and LUM amplitudes exhibit a peak at tooth thicknesses ca. 1.4 - 2.7 mm. Furthermore the LUM amplitude exhibits a small trough at ca. 2.5~3.5 mm; (ii) PTR is sensitive to various defects such as a deep carious lesion, a demineralized area, and a crack while LUM exhibits low sensitivity and spatial resolution.