Micron-sized polyamide 6/12 (PA6/12) copolymer microspheres were firstly synthesized via successive in-situ polymerization of styrene (free radical polymerization), equimolar Laurolactam (LL) and Caprolactam (CL) (anionic ring-opening polymerization). The resulting PA6/12 microspheres were regular sphericity, with diameter ranging from 9.2 to 138.0 microns and narrow size distribution (size distribution ranging from 1.2 to 3.3), as confirmed by scanning electron microscopy (SEM) and Laser diffraction size Analyzer. Furthermore, the study on the PA6/12 microspheres in PA6/12 and PS (PA6/12/PS) blends confirmed that the particle size distribution, diameter of PA6/12 microspheres were controllable, and closely related to the content of PS in the blends, which indicated that the formation of the PA6/12 microspheres in the PA6/12/PS blends can be elucidated via a phase inversion mechanism.