Thalamocortical synapses are key cellular links in sensory, motor and cognitive information processing. In rodents, ventral posteromedial thalamic nucleus (VPM) axons innervate both layer 4 of primary and secondary somatosensory cortex (S1, S2). Posterior thalamic nucleus (Po) projects to the same somatosensory areas as a “higher order” nucleus following a different layer pattern. Despite “primary” and “secondary” functional characterization, it is unknown if differences exist in VPM and Po axon synapse structure and their postsynaptic targets in secondary cortices. Here, we set out to 3D measure and compare the ultrastructure of VPM and Po synapses on these two areas and compare them. We microinjected adult male C57B/L6 mice iontophoretically with biotinylated dextran amine (BDA) in to selectively label thalamocortical axon arborizations. Following a 5 day survival, mice were perfused, and their brains sectioned (50µm) into two parallel series. BDA-labeled cortical arborizations were located on a light-microscopy section series. Adjacent sections were stained for BDA and included for electron microscopy. Area and layer-specific serial images samples were obtained with serial-sectioning TEM or FIB/SEM electron microscopy and subsequently 3D reconstructed and measured. Our results are consistent with previous evidence that VPM axon synapses are mostly located (83-85%) on spiny cell dendrites, while the remaining are dendrite shafts which probably correspond to interneurons. VPMc-S2L4 synaptic boutons are significantly smaller in volume than VPMr-S1L4. Surprisingly, Po-S2L4 boutons show the highest synaptic vesicle count among all datasets. Progress in the description of synaptic circuitry in such areas has a direct impact in sensory integration models.