The standard model of heterotrimeric G protein signaling postulates a dissociation of Gα and Gβγ subunits after activation. We hypothesized that the different combination of lipid-modifications on Gα and Gαβγ subunits directs them into different microdomains. By characterizing rapidly and at high sensitivity 38 fluorescence resonance energy transfer (FRET) pairs of heterotrimeric-G-protein constructs, we defined their microdomains in relation to each other, free from the constraints of the raft/non-raft dualism. We estimated that in a cell ∼30% of these membrane-anchored proteins are mostly clustered in 3400-16,200 copies of 30-nm microdomains. We found that the membrane anchors of Gα and Gαβγ subunits of both the G_i/o and G_q family co-cluster differently with microdomain markers. Moreover, anchors of the Gα_i/o and Gα_q subunits co-clustered only weakly, whereas constructs that contained the anchors of the corresponding heterotrimers co-clustered considerably, suggesting the existence of at least three types of microdomain. Finally, FRET experiments with full-length heterotrimeric G proteins confirmed that the inactive, heterotrimerized Gα subunit is in microdomains shared by heterotrimers from different subclasses, from where it displaces upon activation into a membrane-anchor- and subclass-specific microdomain.