As electronics packages become increasingly thinner and more compact due to size, weight, and performance demands, the use of large intermediate heat spreaders to mitigate heat generation nonuniformities are no longer a viable option. Instead, non-uniform heat flux profiles produced from chipscale variations or from multiple discrete devices are experienced directly by the ultimate heat sink. In order to address these thermal packaging trends, a better understanding of the impacts of non-uniform heating on two-phase flow characteristics and thermal performance limits for microchannel heat sinks is needed. An experimental investigation is performed to explore flow boiling phenomena in a microchannel heat sink with hotspots, as well as non-uniform streamwise and transverse peak-heating conditions spanning across the entire heat sink area. The investigation is conducted using a silicon microchannel heat sink with a 5 × 5 array of individually controllable heaters attached to a 12.7 mm × 12.7 mm square base.