A doubly conditional moment closure (DCMC) with conditioning on normalized total enthalpy and its dissipation rate is presented as an a posteriori predictive modeling tool for ignition of mixtures ethanol and iso-octane with large thermal stratification in homogeneous charge compression ignition conditions. The potential of DCMC for modeling stratified ignitions was evaluated using a direct numerical simulation (DNS). Four two-dimensional DNS cases were selected to evaluate the DCMC model. The DNS cases modeled ignition of various mixtures with high levels of temperature inhomogeneities and with fuels with single-stage and two-stage ignition characteristics. Results showed that DCMC data was in a very good agreement with the DNS data and were significantly enhanced compared to singly conditional moment closure (CMC). A set of a posteriori DNS-DCMS tests was also done to show the significance of various terms in the doubly CMC equations and revealed insignificant effects of the cross dissipation and sources of enthalpy and dissipation rate which can be disregarded from the DCMC equations.