Objectives: This in vitro study investigated the ability of a blue protein-based hydroxyapatite porosity probe to selectively detect artificial enamel caries-like lesions of varying severities.Methods: Artificial caries-like lesions were formed in enamel specimens using a hydroxyethylcellulose-containing lactic acid gel for 4/12/24/72 or 168 h. One untreated group was used as a control. The probe was applied for 2 min and unbound probe rinsed off with deionized water. Surface color changes were determined spectropho-tometrically (L*a*b* color space) and with digital photography. Lesions were characterized using quantitative light-induced fluorescence (QLF), Vickers surface microhardness, and transverse microradiography (TMR). Data were analyzed using one-way ANOVA. Results: Digital photography did not reveal any discoloration in unaffected enamel. However, all lesions stained blue with color intensity positively correlated with demineralization times. The color data reflected similar trends: lesions became significantly darker (L* decreased) and bluer (b* decreased), while overall color differ-ences (AE) increased significantly after probe application (4-h lesion, mean & PLUSMN;standard deviation: AL*=-2.6 & PLUSMN; 4.1/Ab*=0.1 & PLUSMN; 0.8/AE=5.5 & PLUSMN; 1.3 vs. 168-h lesion: AL*=-17.3 & PLUSMN; 1.1/Ab*=-6.0 & PLUSMN; 0.6/AE=18.7 & PLUSMN; 1.1). TMR analysis revealed distinct differences in integrated mineral loss (AZ) and lesion depth (L) between demineral-ization times (4-h lesion: AZ=391 & PLUSMN;190 vol%min x pm/L = 18.1 & PLUSMN; 10.9 & mu;m vs. 168-h lesion: AZ=3606 & PLUSMN;499 vol %min x pm/L = 111.9 & PLUSMN; 13.9 pm). QLF and microhardness were also able to differentiate between deminer-alization times. L and AZ strongly correlated (Pearson correlation coefficient [r]) with Ab* (L vs. Ab*: r=-0.90/ AZ vs. Ab*: r=-0.90), AE (r = 0.85/r = 0.81), and AL* (r=-0.79/r=-0.73).Conclusion: Considering the limitations of this study, the blue protein-based hydroxyapatite-binding porosity probe appears to be sufficiently sensitive to distinguish between unaffected enamel and artificial caries-like lesions.Clinical significance: Early detection of enamel caries lesions remains one of the most critical aspects in the diagnosis and management of dental caries. This study highlighted the potential of a novel porosity probe in detecting artificial caries-like demineralization by objective means.