The causes of compositional diversity in the Tuolumne Batholith, whether source heterogeneity, magma mixing, or fractional crystallisation, is a matter of longstanding debate. This paper presents data from detailed mapping and a microstructural and major element, trace element and isotopic study of an elongate lobe of the Half Dome granodiorite that protrudes from the southern end of the batholith. The lobe is normally zoned from quartz diorite along the outer margin to high-silica leucogranite in the core. Contacts are steep and gradational, except for the central leucogranite contact, which is locally sharp: magmatic fabrics overprint contacts. A striking feature of the lobe is the 18 wt SiO2 range comparable to that observed for the entire Tuolumne Batholith. Feldspar-compatible elements (Sr and Ba) decrease towards the centre, while Rb increases. Light and middle REEs show a smooth decrease towards the centre of the lobe. Calculated initial isotopic ratios of 87Sr/86Sr(i) and εNd(t) have identical values within error across the lobe, except in the central leucogranite, the most silica rich phase, which shows a slightly more crustal signature. Field, structural, geochemical and isotopic data suggest that fractionation was the dominant process causing compositional variation in this lobe. It is envisioned that this fractionation/crystal sorting occurred in a vertically flowing and evolving magma column with the present map pattern representing a cross-section of this column. Thus the areal extent of the lobe represents a minimum size of interconnected melt at the emplacement level of the Tuolumne Batholith and, given its marginal position, limited width and proximity to colder host rocks, implies that fractionation in larger chambers likely occurred in the main Tuolumne Batholith magma chamber(s).