Soft Error Rate (SER) estimation is an important challenge for integrated circuits because of the increased vulnerability brought by technology scaling. This paper presents a methodology to estimate in early stages of the design the susceptibility of combinational circuits to particle strikes. In the core of the framework lies MASkIt , a novel approach that combines signal probabilities with technology characterization to swiftly compute the logical, electrical, and timing masking effects of the circuit under study taking into account all input combinations and pulse widths at once. Signal probabilities are estimated applying a new hybrid approach that integrates heuristics along with selective simulation of reconvergent subnetworks. The experimental results validate our proposed technique, showing a speedup of two orders of magnitude in comparison with traditional fault injection estimation with an average estimation error of 5 percent. Finally, we analyze the vulnerability of the Decoder, Scheduler, ALU, and FPU of an out-of-order, superscalar processor design.