Circulating tumor cells (CTCs) are cancer cells detached from tumors that enter the bloodstream with the rest of the blood cells before settling on remote organs and growing. CTCs play a major role as a target for cancer diagnosis. This study aims to propose and simulate a lab-on-chip (LOC) design that separates CTCs from white blood cells (WBCs) and blood platelets (PLTs) using low-voltage dielectrophoretic separation with high efficiency. The proposed design include two stages a passive and an active one cascaded in a compact package. Numerical simulations are performed on the COMSOL Multiphysics software package to optimize the geometric parameters of the LOC, such as the width and length of the microchannel and the number of electrodes and their arrangements. Moreover, the effects of adjusting the applied voltage values as well as buffer inlet velocity are investigated. The proposed LOC design uses four electrodes at ±2 V to achieve 100% separation efficiency for the three cell types in simulation. The 919 µm × 440 µm LOC has a channel width of 40 µm. The inlet velocities for the blood-carrying cells and buffer are 134 and 850 µm/s, respectively. The proposed LOC can be used for the early detection of CTCs, which can be beneficial in cancer diagnosis and early treatment. In addition, it can be used in cancer prognosis, treatment monitoring and personalizing medicine.