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The incident happened early yesterday and the thieves made off with two cellphones, a tablet and her handbag.
Mokonyane was at the Mthatha Garden Court alongside Nelson Mandela Drive and opposite Walter Sisulu University (WSU) in Mthatha in the Eastern Cape.
The minister was alerted to the burglary after security guards noticed an open window in her room around 1am, said her spokesman Mlimandlela Ndamase.
Ndamase said the minister's room was on the ground floor .
"She is fine now. But she left immediately after the incident was discovered." Mokonyane had reportedly delivered a memorial lecture on the ANC's longest-serving president, Oliver Reginald Tambo, at the WSU on Friday.
The incident came just hours after news on Saturday of a break-in at the offices of the Chief Justice Mogoeng Mogoeng. Asked if the burglary in Mokonyane's room had been an isolated incident or if she had been targeted, Ndamase declined to speculate.
Mthatha police spokesman Lieutenant-Colonel Mzukisi Fatyela confirmed the incident but was unable to say how the thieves had gained entry into the minister's room.
He said a case of housebreaking and theft would be opened.
Hotel manager Andrew Ngwenya promised to forward a written statement regarding the matter, however it had not been received at the time of going to print.