On April 3, Nintendo of America registered the website "supermario4.com", as recently spotted by an IGN reader. Currently, navigating to the site only results in a redirect to Nintendo's main page.
Mario, Luigi, Peach and the rest of the cast have featured in hundreds of games over the years, but the last actually to be given a numbered name of Super Mario Brothers [anything] was Super Mario Brothers 3, which came to the US way back in 1990. (And remains awesome.)
Nintendo head Satoru Iwata revealed back in January that a new, classic-style Mario game was in development, describing it as, "a totally new 2D side-scrolling action Super Mario as a key title for the Nintendo 3DS". The enigmatic "Mario 4" seems likely either to be the 3DS title or to be for the still vaguely mysterious Wii U, due late this year.