Radiation-related caries (RRC) is one of the most significant oral toxicities of head and neck radiotherapy (HNRT); however, the potential of radiation to directly cause harmful dentin and pulpal effects and impair response to caries progression is controversial. Therefore, the aim of this study was to characterize the reactions of the dentin-pulp complex in teeth affected by RRC. Patients and methods: Twenty-two carious teeth extracted from 22 head and neck cancer (HNC) patients were divided into control (conventional caries; n=11) and irradiated (RRC; n=11) groups and paired matched by dental homology, clinical patterns of caries progression following the Post-Radiation Dental Index (PRDI) and microscopic depth of carious invasion. Histopathological characteristics based on morphological hierarchy, cell populations of dental pulp, blood vessels, neural elements, extracellular matrix components, inflammation, patterns of carious invasion and reactionary dentin presence were evaluated by optical light microscopy and histomorphometry. Mean PRDI scores were 3.2 for the control group and 3.8 for the irradiated group. Dentin demineralization patterns were also similar between the groups and the mean depths of demineralization were 1,158.58µm and 1,056.89µm for the control and irradiated groups, respectively. Pulp histopathological changes and dentin reaction patterns were similar between groups and varied according to the PRDI scores and carious lesions depth. Dentin and pulp reactions are highly preserved in RRC teeth.