Background: DFSP is a rare sarcoma, characterized by an indolent course, although local recurrences (LR) and occasional distant metastases (DM) are described. We sought to investigate its natural history and prognostic factors in a large series of patients (pts). Methods: All consecutive pts affected by primary DFSP, located at any sites, treated at Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, from January 1993 to December 2012, were retrospectively reviewed. Overall Survival (OS), surgical margins status, LR and DM were analyzed. Results: 270 pts were identified, 246 (91.1%) affected by classic (C)-DFSP and 24 (8.9%) by fibrosarcomatous (FS)-DFSP. All pts are alive at a median follow-up (FU) of 6 yrs (range 1-15), save for two of them, dead for other diseases. All pts underwent macroscopic complete surgery. Microscopic margins were negative in 247 cases (91.5%), positive (PM) in 23 (8.5%). Overall, LR occurred in 4 pts (1.5%), 2/21 C-DFSP with PM, 2/2 FS-DFSP with PM, respectively. 3 of the LR were located to the scalp, 1 in the groin. A wider resection was repeated on 3 pts, who are disease-free (DF) after 2, 4 and 8 yrs, respectively. One pt refused surgery, her disease is under control with imatinib (IM) after 3 yrs. DM occurred in 3 pts (1.1% of the whole series; 12.5% of FS-DFSP), all affected by FS-DFSP (2 lung and 1 pancreatic metastases). 2 pts were treated with a lung wedge resection. One was DF after 78 mos, the other recurred again after 14 mos and was further treated with a combination of IM and a second surgery. He is still on IM and DF after 6 mos. The last metastatic pts is also on IM and progression-free after 4 mos. Conclusions: Negative margin resection is always curative for C-DFSP, as the observed metastatic risk is nil. PM may be accepted, when cosmesis is an issue, because LR risk remains low and salvaged by a subsequent wider resection. FS-DFSP has a more aggressive course, LR being highly predictable by PM and DM occurring in as many as 12.5% of pts. This should be used to inform treatment decision for the two DFSP variants.