© 2019 IEEE. The co-channel interference (CCI) is one of the major impairments in wireless communication. CCI typically reduces the reliability of wireless communication links, but the »difficult» CCI which is no more or less stronger to the desired signals destroys wireless links despite having myriad of CCI mitigation methods. It is shown in this paper that M-QAM (Quadrature Amplitude Modulation) or similar modulation schemes which modulate information both in in-phase and quadrature-phase are particularly vulnerable to difficult CCI. Despite well-known shortcomings, it is shown in this paper that M-PAM or similar schemes that use a single dimension for modulation provides an important mean for difficult CCI mitigation.