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Recently, we demonstrated that the in situ formation of a building block is an attractive synthesis strategy for creating novel clusters with controllable structures. Herein, we present the design and synthesis of the first tantaloselenite polyoxoanion [Se4(TaO2)6(OH)4O17]4- (1) and a series of lanthanide derivatives (RE3+ = Tb3+, Dy3+, Ho3+, Er3+, Tm3+, Yb3+). In total, we report seven clusters that vary in both composition and structure but which share the same Se4(TaO2)6 building block. The compounds are fully characterized by single-