Multi-port hybrid-based cancellation networks may be used to enable simultaneous transmit and receive in one or more co-existent communication systems. A multi-port hybrid-based cancellation network may include a first and second quadrature hybrid, a first and second two-port network, and other circuitry components. The second quadrature hybrid may be distinct from the first quadrature hybrid. The first two-port network may include a first filter or a first amplifier connected between the first and the second quadrature hybrids. The second two-port network may include a second filter or a second amplifier that is distinct from but essentially the same as the first filter or the first amplifier connected between the first and the second quadrature hybrids. The other circuitry components may be connected between or connected to a connection between one of the quadrature hybrids and one of the two-port networks. These other circuitry components may have a configuration that minimizes signal return loss at least one of the ports of the multi-port hybrid-based cancellation network. They may in addition or instead have a configuration that maximizes signal isolation between at least two of the ports of the multi-port hybrid-based cancellation network.