Holtsville is the location of an IRS Processing Center (which has the lowest assigned numerical ZIP Code, 00501) and is in the Town of Brookhaven and the Town of Islip.
The hamlet known today as Holtsville included only a few farmhouses in the late 18th century. In 1843, the Long Island Rail Road opened its Waverly Station. Maps from that period label the area as Waverly, and a stagecoach line ran north-south along present day Waverly Avenue. As another town named Waverly already existed in Upstate New York, the name of the town was changed to Holtsville in 1860, in honor of U.S. Postmaster General Joseph Holt. As of 1874, Holtsville consisted of 15 houses, a school, and a general store. The train station retained the name "Waverly" for some time, but was eventually also changed to Holtsville, probably in the 1890s, after farmers complained about their shipments going to upstate by mistake. In 1916, the Suffolk County Tuberculosis Sanatorium opened on land that was considered Holtsville at the time, but is now part of the hamlet of Selden. The site later became the location of the main campus of Suffolk County Community College.