The methylenetetrahydrofolate dehydrogenase/cyclohydrolase (MTHFDC) from the thermoacidophilic archaeon Thermoplasma acidophilum is a 30.6kDa molecular-mass enzyme that sequentially catalyzes the conversion of formyltetrahydrofollate to methylenetetrahydrofolate, with a preference for NADP as a cofactor, rather than NAD. In order to elucidate the functional and structural features of MTHFDC from archaeons at a molecular level, it was overexpressed in Escherichia coli and crystallized in the presence of its cofactor, NADP, at 295K using polyethylene glycol (PEG) 4000 as a precipitant. The crystal is a member of the monoclinic space group $P2_1$, with the following unit cell parameters: $a=66.333{AA},;b=52.868{AA},;c=86.099{AA},;and;{eta}=97.570^{circ}$, and diffracts to a resolution of at least $2.40{AA}$ at the synchrotron. Assuming a dimer in the crystallographic asymmetric unit, the calculated Matthews parameter $(V_M);was;2.44{AA}^3/Da$ and the solvent content was 49.7%.