The reaction of Se nanostructures, usually performed using t-Se, with metal cations almost always produces mixed phase metalloid/semiconductor nanostructures. The exception to this is the semiconductor phase that is produced with Ag + ions, where reactions can be executed at much lower temperature and also proceed to completion. The inability of t-Se to react completely with other metal cations may be due to the size of the nanostructures and side product deposition onto the particle surface, which prevents reaction at the metalloid core. Herein, we report the complete conversion of α-SeNPs to semiconductor NPs. The reaction proceeds with a diversity of metal cations, including Pb, Co, Ce, Cu, Ag, Cd, and Zn. We confirmed that the reaction is in situ by comparing EM images of α-SeNPs to selected area electron diffraction patterns (DPs) of MSeNP-converted particles. We further probed the functionality of these particles by co-localizing the EM images and DPs to fluorescence images of ZnSe in particular. As this reaction also works with enzymatically synthesized α-SeNPs, this approach could be adapted to form a contrast marker for correlative light and electron microscopy (CLEM) of biological specimens.