Context : Multiple generations of stars are routinely encountered in globular clusters but no convincing evidence has been found in Galactic open clusters to date . Aims : In this paper we use new photometric and spectroscopic data to search for multiple stellar population signatures in the old , massive open cluster , Melotte 66 . The cluster is known to have a red giant branch wide in color , which could be an indication of metallicity spread . Also the main sequence is wider than what is expected from photometric errors only . This evidence might be associated with either differential reddening or binaries . Both hypothesis have , however , to be evaluated in detail before recurring to the presence of multiple stellar populations . Methods : New , high-quality , CCD UBVI photometry have been acquired to this aim with high-resolution spectroscopy of seven clump stars , that are complemented with literature data ; this doubles the number of clump star member of the cluster for which high-resolution spectroscopy is available . All this new material is carefully analyzed in search for any spectroscopic or photometric manifestation of multiple populations among the cluster stars . Results : Our photometric study confirms that the width of the main sequence close to the turn off point is entirely accounted for by binary stars and differential reddening , with no need to advocate more sofisticated scenarios , such as metallicity spread or multiple main sequences . By constructing synthetic color-magnitude diagrams , we infer that the binary fraction has to be as large as 30 \% and their mass ratio in the range 0.6-1.0 . As a by-product of our simulations , we provide new estimates of the cluster fundamental parameters . We measure a reddening E ( B-V ) =0.15 \pm 0.02 , and confirm the presence of a marginal differential reddening . The distance to the cluster is 4.7 ^ { +0.2 } _ { -0.1 } kpc and the age is 3.4 \pm 0.3 Gyr , which is somewhat younger and better constrained than previous estimates . Conclusions : Our detailed abundance analysis reveals that , overall , Melotte 66 looks like a typical object of the old thin disk population with no significant spread in any of the chemical species we could measure . Finally , we perform a photometric study of the blue straggler star population and argue that their number in Melotte 66 has been significantly overestimated in the past . The analysis of their spatial distribution supports the scenario that they are most probably primordial binaries .