Just over two million Italians aged 15 to 29 or 21.2 percent of young people were neither working nor studying in 2009, Istat said, citing the most recently available data.
Almost a fifth (19.2 percent) of youngsters had left school at 15 or 16 without obtaining a high school diploma, Istat said.
Italy's school drop-out rate compared with an average of 14.4 percent for the 27-nation European Union, Istat noted.
Among people aged 30-34, 19 percent had obtained a degree, against a target of 40 percent set by the European Union for member states to achieve by 2020.
Less than one in two women had a job (44.4 percent), the lowest rate in the EU after Malta, according to Istat's 'We Italians' study.
Italy's rate of long-term unemployed (44.4 percent) is the highest in the EU.
Nationwide, 11.9 percent of people in work were employed off the books, while in Italy's under-developed south, the proportion was 20 percent, Istat said.