Electrospun nanofibers with a coreshell structure or an internal microphase-separated structure were obtained from a homogeneous solution using a conventional single-nozzle electrospinning setup. Because of the poor miscibility of poly(ethylene oxide) (PEO) and chitosan oligosaccharide (CS), the two polymers will separate into a coreshell structure (PEO as core, CS as shell) or an internal microphase-separated structure (PEO as discrete phase, CS as continuous phase) depending on the fraction of each component in the solution. Moreover, the coreshell structure transforms to the internal microphase-separated structure with a continuous decrease of the PEO fraction. The reason for the transition of these internal structures can be attributed to the different phase separation mechanisms. For the coreshell structure, phase separation proceeds in a mechanism of nucleation and growth; however, the internal microphase-separated structure results from spinodal decomposition. Therefore, wide-angle X-ray diffraction and differential scanning calorimetry were employed to investigate PEO crystallization. Since both PEO and CS are biocompatible polymers, together with being able to control the fiber internal structure (coreshell or microphase separation), these electrospun nanofibers will have a great future in the biomedical field. Copyright (C) 2011 Society of Chemical Industry