The soybean cyst nematode (Heterodera glycines) and the closely related sugar beet cyst nematode (Heterodera schachtii) are devastating pathogens of plant roots that use secreted effector proteins to engage in sophisticated host-parasite interactions. While H. schachtii infects and reproduces readily on the roots of Arabidopsis thaliana, H. glycines rarely is able to infect this model plant. The molecular basis for differing host ranges remains obscure but likely involves differences between nematode effector proteins and the recognition of host factors. Recently we reported that constitutive expression of the H. schachtii 10A06 effector protein gene (Hs-10A06) in Arabidopsis affected plant morphology and increased susceptibility to H. schachtii and that the 10A06 protein functions through its interaction with Arabidopsis spermidine synthase 2 (SPDS2). Therefore, we investigated whether differences between cyst nematode effector protein orthologs in two nematode species have a role in mediating host specificity. Here, we show that, similar to Hs-10A06, ectopic expression of H. glycines 10A06 (Hg-10A06) in Arabidopsis affected leaf number and root length, however, to a much lesser extent. More importantly, no effect of Hg-10A06 overexpression on Arabidopsis susceptibility to H. schachtii was observed. While we found that Hg-10A06 can weakly interact with Arabidopsis SPDS2 in yeast-two hybrid assays, this ability to interact with SPDS2 was decreased approximately five-fold compared with Hs-10A06. Collectively, these data suggest that sequence divergence between cyst nematode effector protein orthologs could contribute in determining cyst nematode host range.