Hematological malignancies such as chronic myeloid leukemia and multiple myeloma affect thousands of people annually in the United States. Proliferation of these cancers is in part regulated by the small GTPases. Among the drugs that are used clinically to inhibit GTPase signaling are bisphosphonates, which are used primarily for treatment of bone metastasis and osteoporosis and may have direct anti-cancer effects as well. The bisphosphonates deplete cells of isoprenoid pyrophosphates leading to diminished protein isoprenylation, which is necessary for normal activation of many GTPases. While the clinical nitrogen-containing bisphosphonates diminish both farnesylation and geranylgeranylation, our lab has designed and synthesized a series of novel isoprenoid bisphosphonates that specifically affect protein geranylgeranylation and not farnesylation, including digeranyl bisphosphonate (1) (Bioorg Med Chem, 2006, 14:4130-6). This current study outlines the synthesis and biological activity of various analogs of digeranyl bisphosphonate including olefin isomers and fluorescently tagged bisphosphonates. As with digeranyl bisphosphonate, cells treated with these analogs are depleted of intracellular geranylgeranyl pyrophosphate (GGPP), not farnesyl pyrophosphate (FPP), and protein geranylgeranylation is diminished. The two olefin isomers of digeranyl bisphosphonate are biologically active with little loss of potency. Additionally, this data suggests that fluorescent bisphosphonates can be developed for studies of bisphosphonate localization in cell or animal models.