A reference signal is transmitted on multiple non-contiguous clusters of resources. A user equipment (UE) may be scheduled for data transmission on the multiple non-contiguous clusters, and each cluster may cover a set of contiguous subcarriers. The UE may generate the reference signal based on at least one reference signal (RS) sequence using code division multiplexing (CDM) or frequency division multiplexing (FDM). In a design, the UE generates the reference signal with CDM based on a single RS sequence having a length matching the total length of the multiple non-contiguous clusters. In another design, the UE generates the reference signal with CDM based on one RS sequence for each cluster. In yet another design, the UE generates the reference signal with FDM and transmits the reference signal on a subset of all subcarriers for the multiple non-contiguous clusters.