Autoignition of an n-heptane/air mixture was simulated in nonuniform temperature environments of a rapid compression machine (RCM) and shock-tube (ST) with and without the presence of a cold-spot. The simulations were performed to investigate how the presence of a cold-spot and the cold boundary layer of the chamber wall may affect the ignition delay of the hydrocarbon mixture with negative temperature coefficient (NTC) behavior. The simulations were performed using three models: (1) three-dimensional (3D) computational fluid dynamics (CFD) model, (2) zero-dimensional (0D) homogenous batch reactor model by including the heat transfer model, and (3) 0D adiabatic homogenous batch reactor model. A detailed n-heptane mechanism was reduced in this work and used for 3D combustion modeling. A cold-spot critical radius of 7 mm was determined, which affects the ignition delay by more than 9%. In addition, two combustion modes were observed in the combustion chamber with a nonuniform temperature environment. With the first combustion mode, combustion starts at the high gas temperature region of the combustion chamber and quickly propagates toward the periphery of the chamber. In this combustion mode, the location of the maximum concentration of hydroxyl radical and the maximum temperature are the same. With the second combustion mode, the combustion starts at the periphery of the chamber, where the temperature is lower than the center of the chamber due to heat transfer to the cold chamber wall. The location of maximum concentration of the hydroxyl radical and maximum temperature is different with this combustion mode. The two observed combustion modes are due to the NTC behavior of the n-heptane mixture. The 0D homogenous batch reactor model (with and without heat transfer models) failed to mimic the ignition delay accurately when the second combustion mode was present. In addition, a propagating combustion has been observed in the simulation which is in agreement with some of the optical autoignition diagnostics of these hydrocarbons. This propagating combustion leads to a gradual pressure rise during autoignition, rather than a sharp pressure rise. The results of this work show that 0D homogenous batch reactor models are unable to simulate autoignition of mixtures with NTC behavior.