Abstract Anatectic melt inclusions (nanogranites and nanotonalites) have been found in garnet of kyanite-gneiss at the bottom of the Greater Himalayan Sequence (GHS) along the Kali Gandaki valley, central Nepal, c. 1 km structurally above the Main Central Thrust (MCT). In situ U–Th–Pb dating of monazite included in garnets, in the same structural positions as melt inclusions, allowed us to constrain partial melting starting at c. 41–36 Ma. Eocene partial melting occurred during prograde metamorphism in the kyanite stability field (Eo-Himalayan event). Sillimanite-bearing mylonitic foliation wraps around garnets showing a top-to-the-SW sense of shear linked to the MCT ductile activity and to the exhumation of the GHS. These findings highlight the occurrence of an older melting event in the GHS during prograde metamorphism in the kyanite stability field before the more diffuse Miocene melting event. The growth of prograde garnet and kyanite at 41–6 Ma in the MCT zone, affecting the bottom of the GHS, suggests that inverted metamorphism in the MCT zone and folded isograds in the GHS should be carefully proved with the aid of geochronology, because not all Barrovian minerals grew during the same time span and they grew in different tectonic settings.