This study assessed the efficacy of 60% CPP-ACP to remineralise white spot lesions (WSLs) in enamel and to occlude patent dentinal tubules in a double-blind, randomized, cross-over, in situ study. Human enamel specimens with subsurface lesions (WSLs) and root dentine specimens with open dentinal tubules were prepared and inserted into intra-oral appliances worn by volunteers. Participants wore the appliances 24 h a day for four 14-consecutive day treatment periods with a 7-day washout period between treatments. Four treatments applied with a micro-brush once daily were 60% CPP-ACP with and without 1100ppm F as SnF, 1100ppm F as SnF alone and a placebo as negative control. Mineral content was measured using transverse microradiography and dentine tubules were examined using scanning electron microscopy (SEM). The data were analysed using a repeated measures ANOVA with a Sidak adjustment for multiple comparisons. Once daily application of 60% CPP-ACP with or without SnF produced 36.6 ± 1.6% and 28.8 ± 1.5% remineralisation of the WSLs respectively, and both were significantly higher (p < 0.0001) than that for treatment by SnF alone (8.8 ± 0.7%) or placebo control (2.3 ± 0.4%). SEM analysis of the dentine samples showed that daily application of 60% CPP-ACP with or without SnF produced near complete dentinal tubule occlusion.