Recently, it was documented that the combined treatment of fluoride and laser can induce an even greater increase in caries resistance than laser or fluoride treatment alone. However, the real mechanisms remained unclear. The aim of our present pilot study is to characterize the crystallographic changes in the human enamel treated with fluoride (F), laser (L), and combined fluoride-laser (LF) therapies using Micro-XRD and Micro-FTIR, so as to elucidate the true mechanisms of the combined effects of fluoride and Er:YAG laser on human enamel. Three sound human teeth were selected and 3 windows were created on each tooth surface. The 3 windows were later subjected to the F or L or LF treatment, respectively. The Micro-XRD patterns for the 9 windows were recorded before and after the treatments. Three sections from another 3 sound human teeth were selected for Micro-FTIR investigation and 3 windows were created on the cut surface of each section. The 3 windows were later subjected to the F or L or LF treatment, respectively. The FTIR patterns for the 9 windows were recorded before and after the treatments. The results revealed that both the LF and L treatments caused the contraction in the a-aixs and the improvement in the enamel crystallinity. Though the difference in the a-axis contraction between the LF and L-treated windows was not very significant (0.006Å), this crystallographic change might suggest more than 34% decrease in the enamel solubility. In conclusion, both the L and LF therapies may improve the crystalline stability and thus acid resistance of human enamel.