Equimolar CoCrFeNi is a popular multi‐principal element alloy, generally obtained by melt‐aided routes. The dendritic microstructure of as‐cast alloys is cooling‐rate dependent and thus may show different macromechanical behaviors. Knowledge about the nanomechanics of chemically/structurally distinct zones is important for explaining these differences and facilitating material's design through processing conditions. To this aim, high‐throughput nanoindentation mapping is a potentially powerful tool. However, results are possibly biased by the indentation size effect (ISE) and plastically deformed surfaces induced by inadequate sample preparation. This work is aimed at giving some guidelines for map acquisition and sample preparation based on data from various nanoindentation techniques (i.e., high‐throughput nanoindentation, continuous stiffness, and quasi‐static measurements) collected on differently polished surfaces. It is shown that conventional metallographic preparation leads to a plastically deformed layer that penetrates deep into the surface (11–17 μm). Electropolishing is efficient in removing this layer. However, difficulties may arise due to preferential corrosion in a multiphase system wherefore polishing conditions needs optimization. Nanoindentations of adequately prepared surfaces of CoCrFeNi result in an important ISE, which affects measurements at depths lower than ca 2000 nm. This must be taken into account when performing high‐throughput nanoindentation mapping of this material.